DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s amendment filed 3/2/2026 is acknowledged. Claims 3-4 are canceled.
Applicant’s election without traverse of Group I, claims 1-15, drawn to nucleic acid molecules comprising a nucleotide sequence encoding at least one ASFV antigen and corresponding peptides and immunogenic compositions thereof, and the required species, in the reply filed on 9/16/2025 is acknowledged.
Claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/16/2025.
Applicant elected the following species:
Amino acid sequence of SEQ ID NO: 22 and the corresponding polynucleotide sequence of SEQ ID NO: 21.
Because Applicant canceled the elected species of SEQ ID NO: 22 in claims 14-15, the remaining limitations do not read on the elected species, and thus claims 14 and 15 are hereby withdrawn as being directed to a non-elected species.
The restriction and election of species requirement filed 5/16/2025 indicated that Applicant must elect one or more ASFV antigen amino acid sequences (claims 2, 6, 7, & 14) and their corresponding polynucleotide sequences (claims 4 & 8). Applicant elected a single amino acid sequence (SEQ ID NO: 22) and its corresponding polynucleotide sequence (SEQ ID NO: 21). Claims 6-8 require additional ASFV antigen sequences, and are thus not the elected species.
Claims 6-8 are withdrawn from further consideration as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/16/2025.
Claims 1-2, 5, and 9-13 are under examination on the merits.
Response to Arguments
Applicant’s arguments, see pp. 5-16, filed 3/2/2026, with respect to objection to the drawings and rejections under 35 U.S.C. §§101, 102, 103, and 112(b) have been fully considered and are persuasive. The objection and rejections under 35 U.S.C. §§101, 102, 103, and 112(b) have been withdrawn.
The previous rejection for non-statutory double patenting over copending Application No. 19/483,085 (reference application) in view of Guo (CN 110078801A, published 8/2/2019; machine translation provided due to original document being in the Chinese language) is maintained.
Withdrawn Objections
The following objections are withdrawn due to Applicant’s amendment submitted on 3/2/2026:
Drawings: making reference to colors
Withdrawn Rejections
The following rejections are withdrawn due to Applicant’s amendment submitted on 3/2/2026:
35 U.S.C. §112(b): the rejection of Claims 2, 4, 5, 10, 14, and 15 as being indefinite.
35 U.S.C. §101: the rejection of Claims 1, 3, 5, & 9-12 as being drawn to a naturally-occurring element of nature.
35 U.S.C. §102: Claims 1-5, 9, and 14 under 35 U.S.C. 102(a)(1) as being anticipated by Guo, et al. (CN 110078801A, published 8/2/2019; machine translation provided due to original document being in the Chinese language); Claims 1, 3, 5, and 9-12 under 35 U.S.C. 102(a)(1) as being anticipated by Lopera-Madrid (Vet Immunol Immunopathol. 2017 Mar;185:20-33. doi: 10.1016/j.vetimm.2017.01.004. Epub 2017 Jan 24. PMID: 28241999.
35 U.S.C. §103: Claims 1-5, and 9-15 under 35 U.S.C. 103 as being unpatentable over Lopera-Madrid (supra), as applied to claims 1, 3, 5, and 9-12 above, and in further view of Guo (supra);
Maintained Rejections
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.
(Previous Rejection Maintained) Claims 1-2, 5 & 9-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of copending Application No. 19/483,085 (reference application) in view of Guo (supra). The rejection of claims 3-4 is withdrawn due to cancellation of the claims, and claims 14 and 15 are withdrawn due to Applicant’s amendment to those claims requiring their withdrawal from examination.
Applicant requested the non-statutory double patenting rejection be placed in abeyance until claims have actually issued or are deemed allowable in this application.
Accordingly, the rejection of Claims 1-5 & 9-15 on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of copending Application No. 19/483,085 (reference application) in view of Guo (supra) is maintained.
New Objection
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
The sequence listing is incomplete, and there are SEQ ID NOs: recited in the specification that do not appear in the CRF. Appropriate correction is required.
New Rejections
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.
Scope of Enablement
Claims 1-2, 5, and 9-13 are 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 an isolated nucleic acid molecule comprising at least nucleotide sequence encoding at least one synthetic ASFV antigen, wherein the nucleotide sequence is SEQ ID NO: 21, wherein the nucleotide sequence and ASFV amino acid sequence it encodes are fully defined, does not reasonably provide enablement for similar nucleic acid molecules that are incompletely defined by sequence. 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 or use the invention commensurate in scope with these claims.
The breadth of the claims is found in claim 1.
The nature of the invention is a nucleic acid molecule comprising at least one nucleotide sequence encoding at least one synthetic African swine fever virus antigen, wherein the at least one nucleotide sequence is a nucleotide sequence having at least 90% identity over the entire length of SEQ ID NO: 21, an immunogenic fragment thereof that comprises at least 90% identity over at least 60% of the nucleotide sequence, the nucleotide sequence SEQ ID NO: 21, or an immunogenic fragment of a nucleotide sequence SEQ ID NO: 21, which comprises at least 60% of the full length of the nucleotide sequence (claim 1). Claim 2 requires the nucleic acid molecule to encode at least one peptide comprising an amino acid sequence selected from the group consisting of: an amino acid sequence having at least 90% identity over the entire length of SEQ ID NO: 22, an immunogenic fragment of SEQ ID NO: 22 that comprises at least 90% identity over at least 60% of the amino acid sequence, an amino acid sequence SEQ ID NO: 22, and an immunogenic fragment of SEQ ID NO: 22, that comprises at least 60% of the full length of the amino acid sequence.
The level of skill of one skilled in this art is high.
The specification teaches development of 4 cassettes encoding p32, p54, CD2, and p12, their use in immunizing mice, and testing the serological and cellular responses to the immunization (Figs. 1-11; spec pp. 49-51).
The state of the prior art is such that it is well established in the art that for viral vaccinations, a single amino acid change in the vaccine candidate can render the vaccine ineffective (Kodihalli, et al. J Virol. 1995 Aug;69(8):4888-97. doi: 10.1128/JVI.69.8.4888-4897.1995. PMID: 7609057).
Thus, the state of the art recognized that it would be highly unpredictable that a nucleic acid molecule encoding an ASFV antigen that is mutated or truncated would be effective as an immunogen. One of skill in the art would neither expect nor predict the appropriate functioning of the nucleic acid molecule or antigen that it encodes when mutated and/or truncated.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by Kodihalli, the lack of guidance and direction provided by applicants, and the absence of working examples, undue experimentation would be required to make and use nucleic acid molecules encoding ASFV antigens that are mutated and/or truncated with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed nucleic acid molecules are functional, commensurate in scope with the claimed invention.
Not knowing, absent further experimentation, which modifications function and which do not, when, as set forth above, even a single change of an encoded amino acid can unpredictably affect antigen structure and function, leads to one having no predictability or expectation of success for the function of any given nucleic acid molecule or immunogenic fragment modification. Such random experimentation to identify at a later time what structure or fragment or modification is or is not functional and is embraced by Applicant’s claims is undue experimentation. This affects all claims that can mutate or truncate the nucleic acid or ASFV antigen amino acid sequence, for example claims 1-2, 5, and 9-13.
Moreover, claims not containing elements critical or essential to the practice of the invention, such as nucleic acid molecules or ASFV antigens they encode, which may be broadly mutated or truncated, are not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (18 USPQ 2d 1027 (CAFC 1991)).
Scope of Enablement – Transgenic animal
Claims 1-2, 5 and 11-12 are 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 an isolated nucleic acid molecule comprising at least nucleotide sequence encoding at least one synthetic ASFV antigen, wherein the nucleotide sequence is SEQ ID NO: 21, wherein the nucleotide sequence and ASFV amino acid sequence it encodes are fully defined, does not reasonably provide enablement for non-isolated nucleic acid molecule comprising at least nucleotide sequence encoding at least one synthetic ASFV antigen, wherein the nucleotide sequence is SEQ ID NO: 21, or similar nucleic acid molecules that are incompletely defined by sequence. 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 or use the invention commensurate in scope with these claims.
Regarding claims 1-2, 5 and 11-12, Applicant broadly claims a nucleic acid molecule comprising at least one nucleotide sequence encoding at least one synthetic African swine fever virus (ASFV) antigen (claim 1). The claim reads on a cell within a transgenic animal or a transgene therein given that the term "isolated" is not denoted in describing the host cell, nucleic acid, or vector.
With respect to the unisolated host cells and transgenes as “nucleic acids” of the instant claims discussed above, the state of the art at the time of filing was such that one of skill could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene (Wall et al., Theriogenology, Vol. 45, Pg. 57-68, 1996).
The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene; e.g., specific promoters, presence or absence of introns, etc. (Houdebine et al., Journal of Biotechnology, Vol. 34, Pg. 269- 287, 1994). Furthermore, transgenic animals are regarded to have within their cells, cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappell et al., Current Opinions in Biotechnology, Vol. 3, Pg. 548-553, 1992). Houdebine (Comparative Immunology, Microbiology, and Infectious Diseases, Vol. 32, Pg. 107-121, 2009) teaches progress has been made in the field of transgenic animals for production of foreign proteins (Abstract); however, constructing an efficient expression vector to produce a therapeutic protein is not a standard operation (Pg. 116, Paragraph, second). Therefore, undue experimentation is required to make and use a transgene and transgenic animal to produce the proteins of the instant claims.
Examples in the literature aptly demonstrate that even closely related species carrying the same transgene construct can exhibit widely varying phenotypes. Mullins (1993, Hypertension, Vol. 22, No. 4, pp. 630-633) states that not all animals express a transgene sufficiently to provide a model for a disease as the integration of a transgene into different species of animal has been reported to give divergent phenotypes. For example, several animal models of human diseases have relied on transgenic rats when the development of mouse models was not feasible. Mullins (1990, Nature, Vol. 344, 541-544) produced outbred Sprague-Dawley x WKY rats with hypertension caused by expression of a mouse Ren-2 renin transgene. Hammer (1990, Cell, Vol. 63, 1099- 1112) describes spontaneous inflammatory disease in inbred Fischer and Lewis rats expressing human class I major histocompatibility allele HLA-B27 and human 02- microglobulin transgenes. Both investigations were preceded by the failure to develop human disease-like symptoms in transgenic mice expressing the same transgenes that successfully caused the desired symptoms in transgenic rats (Mullins, 1989, EMBO J., Vol. 8, pages 4065-4072). Thus, the use of nonmurine species for transgenesis will continue to reflect the suitability of a particular species for the specific questions being addressed, bearing in mind that a given construct may react very differently from one species to another.
The examiner notes here, in addition to these issues, even assuming arguendo PHOSITA could make a host organism with functional transgene that encodes the ASFV antigen, there is no predictability that the host will survive its expression. The transgene depends on the host for function and harm to the host, including death, renders the transgene nonfunctional and thus not enabled.
For all these reasons, previously raised and new, transgenes are not enabled.
At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to recite the term "isolated" before the recitation, "nucleic acid molecule" and by amending the polynucleotide claims to specify they are not in a transgenic animal. Applicant may consider using purified in such claims if description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use transgenes and transgenic animals encompassed by the instant claims, with a reasonable expectation of success, absent a specific and detailed description in Applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed nucleic acids and proteins they encode are functional, commensurate in scope with the claimed invention. Thus, claims 1-2, 5 and 11-12 are rejected here.
Written Description
Claims 1-2, 5, and 9-13 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 above are drawn to a genus of nucleic acid molecules comprising at least one nucleotide sequence encoding at least one synthetic African swine fever virus antigen, wherein the at least one nucleotide sequence is a nucleotide sequence having at least 90% identity over the entire length of SEQ ID NO: 21, an immunogenic fragment thereof that comprises at least 90% identity over at least 60% of the nucleotide sequence, the nucleotide sequence SEQ ID NO: 21, or an immunogenic fragment of a nucleotide sequence SEQ ID NO: 21, which comprises at least 60% of the full length of the nucleotide sequence (claim 1). Notably, although nucleotide sequences may be immunogenic due to being observed by the immune system, that is independent of their sequence. Nucleic acids encode proteins that are specifically immunogenic.
Even if the prior art is aware of such nucleic acids that encode ASFV antigens, the totality of known immunogenic fragments of a nucleotide sequence would not be representative of the entire genus for the reasons discussed below.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
Furthermore, to satisfy the written description requirement for the genus nucleic acid molecule comprising at least one nucleotide sequence encoding at least one synthetic African swine fever virus (ASFV) antigen, Applicant must adequately describe representative nucleic acid molecules to reflect the structural diversity of the claimed genus. See Eli Lilly, 119 F.3d at 1568 (“[N]aming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993) (“Claiming all DNA[s] that achieve a result without defining what means will do so is not in compliance with the description requirement; it is an attempt to preempt the future before it has arrived.”).
MPEP § 2163 states that 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, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, as here in which the nucleic acid molecules (e.g., claim 1) and encoded peptides (e.g., claim 2) claimed can have sequence variation, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” One of skill in this art cannot envision the structure of every nucleic acid molecule comprising at least one nucleotide sequence encoding at least one synthetic ASFV antigen, wherein the nucleotide sequence may be an immunogenic fragment comprising at least 90% identity over at least 60% of the nucleotide sequence, or an immunogenic fragment of an amino acid sequence of SEQ ID NO: 22 wherein the immunogenic fragment comprises at least 90% identity over at least 60% of the amino acid sequence. The specification describes development of 4 cassettes encoding p32, p54, CD2, and p12, their use in immunizing mice, and testing the serological and cellular responses to the immunization (Figs. 1-11; spec pp. 49-51). However, the specification does not demonstrate any evaluation of the consequences of mutating the cassettes encoding the antigens or truncation of up to 40% of the nucleic acid molecules or antigens they encode. Therefore, since limited species are provided to represent these genera, the claims encompassing the same clearly fail the written description requirement.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members.
“Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus. Four expression cassettes, without mutation or truncation, is certainly not adequate. The disclosure does not provide examples of other mutants or truncations that confer the required function.
Overall, at the time the invention was made, the level of skill for preparing nucleic acid molecules encoding antigens and immunogenic peptides was high.
A representative number of species has not been taught to describe these genera; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genera of nucleic acid molecules encoding ASFV antigens. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
While applicant has described a few species within each of the genera recited, and the art may provide more, the genus is large and would encompass structures that cannot be visualized from the prior art or instant disclosure. One of skill in this art cannot determine the structures encompassed by the claimed genera only defined by function. Any future ASFV antigen structure may or may not be encompassed, and if it is, it would not have been represented in Applicant’s disclosed species. Thus, the described species cannot be considered representative of the recited genera of nucleic acid molecules encoding ASFV antigens. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, the claims are rejected here.
As discussed above, an applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613. Therefore, it is recommended that the instant claims be amended to recite complete structural information of the claimed nucleic acid molecules and ASFV antigens that they encode, including full sequences and precise positions of the proline substitutions.
Claim Rejections – Improper Markush Grouping
Claims 1-2, 5, and 9-13 are rejected on the judicially-created basis that they contain an improper Markush grouping of alternatives.
See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial structural feature and a common use that flows from the substantial structural feature for the following reasons:
MPEP 803.02 provides guidance on the analysis of a proper Markush group. Members of a proper Markush group are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed relationship, and it is clear from their very nature or from the prior art that all of them possess this property. The MPEP further provides that in the members of a proper Markush group there should be (1) a common utility, and (2) a substantial structural feature essential to that utility.
In the instant case, claims 1-2, 5, and 9-13 include the group of nucleic acids encoding synthetic ASFV antigens, but they do not appear to share a substantial structural feature. Thus, a common use cannot flow from a shared substantial structural feature in these claims. Since the instant claims contain Markush groups with members of nucleic acids encoding synthetic ASFV antigens lacking shared, discernable, discrete domains associated with the claimed function of ASFV antigens, the claims contain an improper Markush group and are rejected here. Additionally, each nucleic acid sequence encodes a distinct ASFV protein (spec., p. 35). These are unrelated sequences that correspond with distinct chemical, structural, and functional characteristics, and do not share a substantial structure. Furthermore, the claims allow for large variation within the sequences themselves (e.g., 90% identity over at least 60% of the nucleotide sequence of SEQ ID NO: 21), which further adds to different structural requirements of the members of this improper Markush group.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 5, and 9-13 are rejected under 35 U.S.C. 103 as being unpatentable over Lopera-Madrid (Vet Immunol Immunopathol. 2017 Mar; 185:20-33. PMID: 28241999) in view of Guo, et al. (CN 110078801A, published 8/2/2019; machine translation provided due to original document being in the Chinese language), Lokhandwala, et al. (Clin Vaccine Immunol. 2016 Nov 4;23(11):888-900. doi: 10.1128/CVI.00395-16. PMID: 27628166), and Genscript (GenScript Codon Usage Frequency Table Tool, published 2/9/2019 at https://web.archive.org/web/20190209075318/https://www.genscript.com/tools/codon-frequency-table, 3-page printout, accessed 7/10/2026).
The Prior Art
Lopera-Madrid teaches mammalian cell derived and Modified Vaccinia Ankara (MVA) vector African swine fever virus subunit antigens in swine (Title). Lopera-Madrid further discloses that MVA-vectored CD2v (also called EP402R) resulted in interferon-gamma spot forming cell responses and T-cell proliferative responses against CD2v (Abstract; Fig.5). Lopera-Madrid teaches that MVA-ASFV constructs were administered IM at 10⁷ TCID₅₀ in 1 ml dose of Tris 1 mM (pH 9.0; p. 22, col. 2, para. 5), and generation of MVA-ASFV viruses (p. 24, col. 2, para. 1). The CD2v MVA vector would inherently possess DNA and a start codon linked to the CD2v expression cassette because MVA is DNA virus and CD2v is expressed from the viral infection, respectively. Lopera-Madrid also discloses administration of sub-unit vaccines with TS6 adjuvant (p. 22, col. 2, last para.), administration of MVA-ASFV constructs with Tris 1 mM (pH 9.0), and that adjuvant systems were used in conjunction with an adenovirus-vectored study (p. 31, col. 1, para. 2).
However, Lopera-Madrid does not teach a nucleic acid sequence having at least 90% identity over the entire length of SEQ ID NO: 21, a nucleotide sequence comprising at least 90% identity over at least 60% of SEQ ID NO: 21, SEQ ID NO: 21, or a nucleotide sequence that comprises at least 60% of the full length of the nucleotide sequence of SEQ ID NO: 21. Nor does it disclose the ASFV sequence SEQ ID NO: 22 or variants thereof over 60% of the full length of the amino acid sequence or 90% identity over the full length or 60% of the full length of the amino acid sequence.
Guo teaches a recombinant plasmid encoding African Swine Fever Virus (ASFV) CD2v, which has a sequence identical to SEQ ID NO: 22 (Guo SEQ ID NO: 2; fragment SEQ ID NO: 4 of Guo lacks the C-terminal 150 amino acids; p. 3; Abstract). Additionally, Guo's CD2v construct possesses a start codon (Guo SEQ ID NOs: 2 & 4), and is configured for expression in CHO cells (Abstract). Furthermore, Guo discloses that by truncating the 150 amino acids of ASFV CD2v, it helps the protein to better fold, exposing antigenic sites therein (p. 3).
Accordingly, an immunogenic composition encoding SEQ ID NO: 22 would have been obvious to one of ordinary skill in the art.
Lokhandwala teaches adenovirus-vectored ASFV formulated in adjuvant to immunize swine against ASFV (Abstract). Lokhandwala specifically discloses codon optimization for protein expression in the swine host, wherein DNA plasmid constructs, recombinant adenoviruses, and recombinant baculoviruses contain optimized synthetic genes for amino acid sequences of ASFV antigens (p. 889, col. 1, last para.; p. 889, col. 2, para. 1).
Genscript teaches a Codon Usage Frequence Table Tool, which has the frequency information for each codon in expression host organisms Pig, Escherichia coli, and human, among others (p. 1).
It would have been obvious to one of ordinary skill in the art to modify the ASFV CD2v-encoding MVA vectors taught by Lopera-Madrid to incorporate genes encoding the CD2v amino acid sequences identical to the instant SEQ ID NO: 22. It would have been further obvious to codon optimize the ASFV antigen SEQ ID NO: 22 sequence, arriving at SEQ ID NO: 21. As demonstrated by Lokhandwala, codon optimization allows for protein expression in the swine host for ASFV-antigen encoding genes. Because the codon tables are well known in the art, as disclosed by Genscript, it would have been obvious to one of ordinary skill in the art to optimize the SEQ ID NO: 22-encoding gene to be SEQ ID NO: 21, with a reasonable expectation of success. In addition, since all codons are known for each amino acid, all combinations of codons to produce a known protein are obvious and will encode said protein with a very high expectation of success, arriving at predictable results. It also would have been obvious for the nucleotide sequence to be operably linked to a start codon, since it would be necessary for expression of the antigen and is inherent to the constructs disclosed by the cited references. Additionally, the cited references each disclose expression vectors encoding ASFV antigens, so it would be obvious to adapt them to comprise SEQ ID NO: 21, which encodes SEQ ID NO: 22. Additionally, it would have been obvious to one of ordinary skill in the art that the nucleic acid molecule is incorporated into a viral particle, because Lopera-Madrid teaches recombinant MVA viruses encoding ASFV antigens. Use of a pharmaceutically acceptable excipient, which the spec indicates can include vehicles, adjuvants, carriers or diluents (p. 40), also would have been obvious to one of ordinary skill in the art, since the vaccines disclosed by Lopera-Madrid are administered with TS6 adjuvant or Tris buffer. It also would have been obvious to one of ordinary skill in the art to administer the MVA vectors with an adjuvant, as Lopera-Madrid discloses administration of other vaccines with TS6 adjuvant.
One of ordinary skill in the art would have been motivated to vaccine against ASFV. There would be a reasonable expectation of success because Lopera-Madrid discloses use of such compositions in swine. Therefore, claims 1-2, 5, and 9-13 were prima facie obvious before the priority date of the instant invention.
Applicant presents the following arguments to the previous rejection under 35 U.S.C. §103 as being unpatentable over Lopera-Madrid (Vet Immunol Immunopathol. 2017 Mar; 185:20-33. PMID: 28241999) in view of Guo, et al. (CN 110078801A, published 8/2/2019; machine translation provided due to original document being in the Chinese language), which was withdrawn in this action but are still relevant to the new rejection under 35 U.S.C. §103 as being unpatentable over Lopera-Madrid (Vet Immunol Immunopathol. 2017 Mar; 185:20-33. PMID: 28241999) in view of Guo, et al. (CN 110078801A, published 8/2/2019; machine translation provided due to original document being in the Chinese language) and Lokhandwala, et al. (Clin Vaccine Immunol. 2016 Nov 4;23(11):888-900. doi: 10.1128/CVI.00395-16. PMID: 27628166).
Applicant’s arguments Applicable to the new ground of rejection:
Applicant submits that even given SEQ ID NO: 22 from Guo, as a starting point, one of skill in the art could not have arrived at the present invention through routine optimization with a reasonable expectation of success. The degeneracy of the genetic code, while offering flexibility, introduces a vast number of possible nucleotide sequences that can encode the same amino acid sequence. Generation of an optimized sequence is not a routine matter but is necessarily an inventive process as it requires an inventor to provide input at multiple levels to achieve a desired result. One of skill in the art would have to attempt thousands of different codon permutations and validate the expression levels and immunomodulation properties of each of the resulting sequences. Because of this inherent unpredictability a skilled person would not have any expectation of success at arriving at the claimed invention in view of Guo and Lopera-Madrid. As such, Applicant submits that the sequences recited in the instant claims involve a high level of creative design input and are inventive.
After careful consideration, Applicant’s arguments are found to be unpersuasive:
While it is true that the degeneracy of the genetic code allows for a large number of possible nucleotide sequences to encode a 359-amino acid long protein (like SEQ ID NO: 22), or a 216-amino acid long protein (approximately 60% of the full length SEQ ID NO: 22), there would have been a reasonable expectation of success in one of ordinary skill in the art arriving at SEQ ID NO: 21. As demonstrated by Lokhandwala, codon optimization of ASFV genes for expression in a mammalian cell or a swine host is known in the art. Additionally, the claims do not require particular expression levels or immunomodulation properties. Any foreign gene expressed in a host would exhibit some level of immunogenicity, even if expressed at a low level.
Conclusion
No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is 571-272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at 571-270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671
/Michael Allen/Supervisory Patent Examiner, Art Unit 1671
Prosecution Insights