Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/17/2025 has been entered.
Claims 42-61 are now pending. Claims 52 is amended. Claims 42-61 are currently under prosecution.
Claim Rejections - 35 USC § 112
Maintained Rejection
(Arguments Addressed)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 42-61 remain 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. This is a WRITTEN DESCRIPTION Rejection.
The claims are drawn to a recombinant poxvirus comprising heterologous acid sequences, each heterologous nucleic acid sequence encoding a neopeptide fusion comprising 2 to 15 neopeptides, wherein at least 60% of said 2 to 15 neopeptides comprise a missense or a frameshift mutation, wherein each neopeptide fusion has a negative hydrophobicity score and/or a hydropathy score equal or below 0.1, and wherein two or three heterologous nucleic acid sequences encode a neopeptide fusion in which: (1) each neopeptide fusion comprises 5 to 10 neopeptides; (2) each neopeptide fusion comprises linkers at the N-terminus of the first neopeptide, and between each neopeptide; and (3) each neopeptide fusion comprises a signal peptide at the N terminus of said fusion; and (4) each neopeptide fusion does not contain a predicted transmembrane segment. Thus, the claims require selecting neopeptides based on hydrophobicity values and lack of transmembrane segments.
It has been interpreted that one of skill in the art cannot construct a peptide without knowing what the amino acid structure of that peptide is. It is not clear how one can make and administer a peptide without knowing the amino acid structure of that peptide. It also has been interpreted that a personalized vaccine comprising neopeptides capable of inducing an immune response in a patient. The definition of vaccine in the online Merriam-Webster on-line dictionary is a preparation that is administered (as by injection) to stimulate the body's immune response against a specific infectious agent or disease.
The instant specification discloses a list of 18 neopeptides (Table 2), a list of four recombinant MVA that were generated (Table 4), and three total fusion neopeptides (Table 6). The specification also discloses solubility evaluations of three viral genomes of neopeptides as shown in Tables 6-8. The specification does not provide adequate written description of the claimed genus of neopeptide fusions comprising a negative hydrophobicity score below 0.1. The specification does not provide SEQ ID NOs: for the neopeptides, nor are any of the neopeptides sequences are claimed. Although the specification discloses neopeptides using algorithms for tumor specific mutations, the claims encompass all neopeptides discovered in the future. Furthermore, the specification does not disclose which peptides are capable of inducing an immune response.
One could only identify the amino acid structures of neopeptides in other cancer patients by sequencing the genome, exomes or transcriptomes from the other patients and using algorithms to determine candidate neopeptides. It has been interpreted that one of ordinary skill in the art would not be in possession of the neopeptides to be used in a personalized cancer vaccine from all cancer patients by knowing the structure of neopeptides to be used in cancer specific vaccine from a few cancer patients from one type of cancer.
A peptide is defined by its amino acid sequence or by sufficient characteristics that one of ordinary skill in the art would be able to identify the specific peptide. Peptides vary in their amino acid sequences and knowledge of the amino acid sequence of one peptide does not identify the amino acid sequence of a second peptide in the absence of sufficient structural identity or identifying characteristics. This is similar to what was indicated in Amgen Inc vs Sanofi ( 2017-1480, Fed Cir, 2017) that the disclosure of a well characterized antigen is insufficient for an adequate written description of the antibody that binds the antigen. The Court stated that “an adequate written description must contain enough information about the actual makeup of the claim products — a precise definition such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other material,” which may be present in “function “terminology “when the art has established a correlation between structure and function” (page 17, 1St paragraph). The Court went on to indicate that knowledge of the chemical structure of an antigen does not tell you anything about the structure of the antibody (Id).
The specification does not provide adequate written description of the claimed genus of neopeptides and neopeptide fusions that are capable of functioning in a vaccine. The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the Applicant had possession at the time of invention the genus of nucleic acids encoding neopeptides in an individual that is capable of functioning in a vaccine.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, 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 genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Fri. January 5, 2001, see especially page 1106 column 3).
The specification does not provide adequate written description of the claimed invention. The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the Applicant had possession at the time of invention of the claimed invention, the genus of neopeptide fusions with a negative hydrophobicity score and/or hydropathy score equal to or below 0.1, and no transmembrane segments. Furthermore, the genus of neopeptides in an individual are claimed by function, the capability of functioning in a personalized cancer vaccine. Thus, the neopeptides are claimed by their capability of inducing an immune response in a cancer patient. Thus, out of an unknown and likely very large number of neopeptides capable of being used in a vaccine, the specification only discloses neopeptides from a handful of gene fusions capable of being used in a vaccine that were already known in the art.
The Federal Circuit addressed the application of the written description requirement to DNA-related inventions in University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997). The court stated that “[a] written description of an invention involving a chemical genus, like a description of a chemical species, requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials.” Id. At 1567, 43 USPQ2d at 1405. The court concluded that “naming 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.” Id.
The Federal Circuit clarified that a molecule can be adequately described without disclosing its complete structure. See Enzo Biochem, Inc. V. Gen-Probe Inc., 296 F.3d 1316, 63 USPQ2d 1609 (Fed. Cir. 2002). The Enzo court adopted the standard that the written description requirement can be met by “show[ing] that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics ....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. “ Id. At 1324, 63 USPQ2d at 1613.
Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. The court in In re Alonso (Fed. Cir. 2008) citing In re Enzo, Enzo, 323 F.3d at 969 stated that [F]or purposes of satisfying the written description requirement, it is not enough merely to disclose a method of making and identifying compounds capable of being used to practice the claimed invention.
It is noted that AbbVie v. Janssen Biotech and Centocor Biologics (Fed. Cir. 2014) confirms a strong Post-Ariad Written Description requirement - especially with regard to genus-species claim situations. In the decision, Judge Lourie focuses particularly on the alleged infringing antibodies and notes that: [While] AbbVie patents need not describe the allegedly infringing [compound] in exact terms . . . [t]he patents must at least describe some species representative of antibodies that are structurally similar to [the accused compound]. Because the patent document lacked any such structural description, the court confirmed that the corresponding claims were invalid under 112(a). In discussing the case, Judge Lourie was clear that one problem here is that the invention was described in terms of its function rather than its structure. Lourie writes:
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.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed or through disclosure of a functional characteristic of the claimed genus coupled with a known or disclosed non-functional characteristic (structure) that correlates to the function.
Alternatively, per Enzo, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.
In this case, the specification does not describe the genus of that are capable of functioning in a vaccine that satisfies either the Lilly or Enzo standards. The specification does disclose art which demonstrated neopeptides in a fusion and four recombinant MVA. However, the specification does not appear to disclose any neopeptides that are capable of inducing an immune response in a cancer patient that were not already known to be immunogenic. Thus, out of an unknown and likely very large number of neopeptides capable of being used in a vaccine, the specification only discloses neopeptides from a handful of gene fusions capable of being used in a vaccine that were already known in the art. The specification does not disclose sufficient examples of neopeptides that are capable of functioning in a vaccine.
Thus, the specification does not provide an adequate written description of the genus of neopeptides that is required to practice the claimed invention. The instant disclosure does not adequately describe the scope of the claimed genus, which encompasses a substantial variety of subgenera. Since the disclosure fails to provide sufficient relevant identifying characteristics, and because the genus is highly variant, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Response to Arguments
Applicant submits specific cases of claims reciting inventions using neoantigens, and stated that the Office has repeatedly found that the genus of neoantigens is within the knowledge of persons of ordinary skill in the art and need not to be determined afresh.
Applicant’s arguments have been considered but are not persuasive. The claims are directed to a composition that relies on identification of neopeptides for the recombinant poxvirus. The claims recite a” recombinant poxvirus comprising heterologous nucleic acid sequence, wherein each heterologous nucleic acid sequence encodes a neopeptide fusion comprising 5 to 10 neopeptides, wherein at least 60% of said 5 to 10 neopeptides comprise a missense or a frameshift mutation…” The specification defines neoantigens as “The term “neoantigen” as used herein refers to an antigen that has emerged during the carcinogenesis process in a cancer cell. In a preferred embodiment, a neoantigen comprises one or more non-silent mutation(s) of amino acid residue(s) with respect to a corresponding wild-type antigen.” [0056] One of ordinary skill in the art cannot envision what the neopeptides are that is required by the recombinant poxvirus.
As noted before, the issue is not whether the Applicant can identify and select neopeptides for the recombinant poxvirus, but whether the specification has possession of the genus of peptides and epitopes with one or more non-silent mutation that emerged during carcinogenesis. The specification does not describe a sufficient number of peptides to demonstrate possession of the genus. The specification only discloses neopeptides form a handful of gene fusions capable of used in a vaccine that are already known in the art.
It is known that there are challenges for identifying neoantigens that one of ordinary skill in the art cannot select any neopeptide. Garcia-Garijo A et al. (Frontiers in Immunology 2019 10 1-19; of record) recognizes these challenges and that that whether individualized immunotherapies targeting neoantigens can mediate effective antitumor responses in a broader patient population, remains an open question. Garcia-Garfijo further teaches that “despite all the technological innovation and development of novel screening assays, the rapid and precise identification of the bona fide neoantigens in any given patient remains a major hurdle that will need to be overcome to translate the potential of neoantigen targeting into effective therapies for patients with cancer.” [pg 5]
Contrary to Applicant’s arguments, one of ordinary skill in the art would not be in possession of the neopeptides to be used in a personalized cancer vaccine from all cancer patients by knowing the structure of neopeptides to be used in cancer specific vaccine from a few cancer patients from one type of cancer.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/JANET L EPPS -SMITH/Supervisory Patent Examiner, Art Unit 1646