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 election without traverse of Group I (claims 295-306) and the species of: polynucleotide as agent type (claim 295ii); neoepitope of SEQ ID NO. 1131 encoded by frameshift I462fs-1 of SEC31 gene, wherein said epitope binds HLA-A03:01; and Lynch syndrome as target disease, in the reply filed on 08/18/2025 is acknowledged.
Claims 307-315 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/18/2025.
Claim Status
Claims 1-294 are canceled.
Claims 307-315 are withdrawn.
Claims 295-306 are under examination.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The use of the term BITE (0030), marks in 0039, marks in 0083, marks in 0546-0547, 0320, and 0552, FLAG (0320), and SEPHAROSE (0382), each of which is a trade name or a mark used in commerce, has been noted in this application. Each term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 295-297 are objected to because of the following informalities: these claims all contain periods after letters. However, the only periods permitted in claims are at the end and after abbreviations. All periods otherwise should be changed to right parentheses, for example.
Appropriate correction is required.
Claim Interpretation
The examiner notes that I462fs-1 is readable to a PHOSITA. Isoleucine at some position 462 is affected by a frameshift (fs) which causes the residue to be read from the third position of the codon (-1) instead of the first position thereof. Thus, it is a two base deletion.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 296 and 300 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.
Claim 296 recites position I462. However, the claim does not set forth a sequence identifier with this position. Thus, it has multiple interpretations. SEC31 protein has 19 isoforms of different lengths. It is also a transporter and so must be targeted by signaling sequence to a membrane. For both these facts, see Uniprot (Entry O94979, SC31A_HUMAN, downloaded 09/19/2025). Later processing of such a signal peptide would change position 1. Thus, which position is 462 has different interpretations depending on the isoform and maturity of the protein. The presence of multiple structural interpretations renders the claim indefinite.
See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) ("[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.").
It is recommended that Applicant refer to position 462 of a sequence identifier in a wherein clause after the frameshift information.
Claim 300 depends on itself which is improper and so its metes and bounds are not clearly set forth and it is rejected here. It will be interpreted to depend on claim 295 for this examination.
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 295-296 and 298-306 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 polynucleotides encoding tumor-specific, antigenic epitopes from the gene SEC31A. They are defined by no sequence in these claims but only function (encoding peptides with antigenicity, tumor-specificity and/or vaccine capacity). When one goes to the specification to identify a representative species of this genus, they find only nucleic acids that encode the peptides of SEQ ID Nos. 105, 106 (0227), or fragments of SEQ ID NO. 106 as in claim 297e. Thus, Applicant has only provided two peptides with tumor-specific epitopes to represent the genus of peptides encoding by the polynucleotides claimed and thus the genus of polynucleotides recited. It is also noted that these two peptides are highly related/similar and all fragments of SEQ ID NO. 106 of claim 297, while there are 12 of them, they are all very similar and from the same stretch of one SEC31a frameshift mutant. Thus, Applicant teaches only, at most 14 highly related species to represent the recited genus. These species are not sufficient to represent such a broad genus.
Even if the prior art is aware of additional SEC31A variants caused by frameshifts that are tumor specific, the totality of known variants that meet the required functions would not be representative of each the 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.
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 polynucleotide can encode a peptide of any sequence so long as it is from a frameshifted SEC31A gene, one must describe a sufficient variety of species to reflect the variation within the genus. However, only two related peptides are provided and fragments residing in one of them. SEC31A is a large protein of 1220 residues. Thus, the genus of frameshifted SEC31A peptide is enormous. Yet, one of skill in this art cannot envision the structure of any other tumor-specific epitopes, and nucleic acids encoding the same, other than those taught by Applicant. There is no guarantee there are many others. There is no way to predict where a frameshift mutation may occur. There is equally no way to no if such a mutation would be linked to cancer in such a way as to be tumor specific and a possible immunogen for vaccination. All this requires guidance by Applicant or future research to uncover. The future does not provide written description for this application and so Applicant and the prior art are the only sources of such polynucleotides/peptides. As for specific species, Applicant only provides explicit teaching of such. Thus, PHOSITA can only envision the structure of the species taught by Applicant and would only consider Applicant in possession of the same, no more. Therefore, since only 14 highly related species are provided to represent the genus recited, 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).
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. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“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). Since the peptide structure is responsible for its antigenicity and tumor-specificity, and said structure varies between T-cell epitopes, there is no correlation between structure and function between the members of such a large T-cell epitope genus as currently recited. The group need have no common structure at all. Thus, functional language should not be used to define the genus. Rather, structure should be used.
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. Fourteen highly similar and related species is certainly not adequate just as the related species of Joe-9 derivatives above were inadequate.
Overall, at the time the invention was made, the level of skill for identifying cancer-specific T cell epitopes was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify such epitopes of SEC31a with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
Since only a few related species of SEC31a peptides with tumor-specific epitopes are taught, the instant claims above clearly fail the written description requirement. A representative number of species has not been taught to describe the genus of polynucleotides encoding such peptides. While Applicant has described a few species within each of the genus recited, each genus is very large and would encompass epitopes and polynucleotides encoding the same that cannot be visualized from the prior art or instant disclosure. Any future 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 genus. 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 only a functional SEC31a T cell epitope identified by Applicant.
Claims 299-300 and 305 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 immunogenic compositions comprising polynucleotides that encode T-cell epitopes of SEC31a and pharmaceutical compositions with said nucleic acids and an adjuvant, does not reasonably provide enablement for vaccine comprising the same or a pharmaceutical composition with such a nucleic acid that lacks adjuvant. 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 299 which recites a composition with a polynucleotide that encodes a tumor-specific T cell epitope from SEC31a mutated by frameshift that is a vaccine.
The nature of the invention is an immunogenic composition to treat cancers that express the SEC31a frameshift variants taught by Applicant.
The level of skill of one skilled in this art is high.
The specification teaches that vaccines are prophylactic (0137). However, the specification fails to show any experiments that conclude any disease can be treated with the recited vaccines. Importantly, Lynch Syndrome is a colorectal cancer with hereditary pathology. Thus, all product claims that recite vaccines assert capacity to prevent cancer.
No material has been found to date that has been shown to or would be expected to prevent cancer, and there is no working example, prior art, or any evidence that would provide the skilled artisan with any predictable guidance to use the claimed invention. It would be reasonable to conclude the claimed invention is not enabled.
Reasonable guidance with respect to preventing any cancer relies on quantitative analysis from defined populations that have been successfully pre-screened and are predisposed to particular types of cancer. This type of data might be derived from widespread genetic analysis, cancer clusters, or family histories. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical cancer 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.
The vaccine art teaches that compositions comprising some tumor associated antigens are effective in treatment of cancer through generation of immunogenic response to the tumor antigen (see for example, Komenaka et Al., Clinics in Dermatology, 2004, Vol. 22, Pg. 251-265, specifically page 257). However, nowhere in the art does it show that tumor antigens are effective at preventing cancer. Evans et Al. (Q. J. Med 1999: 92: 299-307) teach that vaccines against cancer are not fully established, and it is stated that adjuvant therapy to prevent or delay disease still needs experimentation. Evans et Al. further state that such cancer vaccines are at best used as a therapeutic and not as a prophylactic and that “the notion that cancer vaccines will replace standard therapeutic strategies in malignant disease still belongs to the realm of fiction” (see page 303 last paragraph).
In some cases, it is known that certain cancers arise from a single cause. This cause can be viral as in the case of cervical cancer, caused predominantly by persistent cervical infection with human papillomavirus (HPV) (Schiffman et Al., The New England Journal of Medicine, Vo. 353, No. 20, Pg. 2101-2104, 2005). Schiffman et Al. teach that primary prevention through vaccination against HPV might be possible in young women (Pg. 2101, Column 3, Paragraph, first parital). However, they also teach that vaccine evaluations are ongoing (Pg. 2103, Column 3, Paragraph, first full). In addition, the most promising vaccines designed against HPV types 16 and 18 would only prevent 70 percent of cervical cancer cases at best (Pg. 2103, Column 2, Paragraph, first full). Therefore, there is still no vaccine that can definitively prevent a cancer. Current evidence points only to the potential of future prophylactic agents.
The art of small molecule chemotherapeutics teaches that some molecules successful at treating cancers can also reduce risk. Cuzick et Al. (The Lancet, Vol. 361, Pg. 296-300, 2003) teach that tamoxifen can reduce the risk of ER-positive breast cancer but cannot be recommended as a preventive agent (Pg. 299, Column 2, Paragraph, first). The reason it cannot be recommended centers around the need for continued research into specific subgroups of high-risk but healthy women for whom the risk-benefit ratio is sufficiently positive to recommend prophylactic tamoxifen treatment (Pg. 299, Column 2, Paragraph, first).
With respect to peptide-based cancer prevention agents, the art currently does not recognize a definitive example though promising candidates are present. Hernandez-Ledesma (Peptides, Vol. 30, Pg. 426-430, 2009) teaches that lunasin, a peptide discovered in soy has demonstrated cancer-preventative capacity in vitro and mouse models (Abstract). The authors define it as a perfect candidate to exert an in vivo cancer-preventive activity but more research is required to establish it in this role (Pg. 429, Column 2, Paragraph, first partial).
Therefore, the art has only recognized the treatment of a cancer.
The specification teaches tumor vaccines are typically composited of antigens and adjuvants (0003). It states that effective vaccines may require a strong adjuvant to initiate immune response (0163).
With respect to the use of a vaccine without an adjuvant, Sun (Vaccine, Vol. 21, Pg. 849-855, 2003) teaches the activation of antigen-specific T cells of an appropriate phenotype is central to effective vaccination. Although a complicated decision process underlies this process, a number of signals have been identified which are necessary for T cell activation and differentiation. Signal 1 is the cognate signal delivered to T cells by peptide/MHC Class II complexes on the surface of antigen presenting cells (APCs). Identification of pathogen-derived antigens that provide the appropriate cognate signals to T cells has occupied a great deal of vaccine development activity. However, Signal 1 is usually inadequate for effective vaccination without the presence of Signal 2, the co-stimulatory molecules or cytokines produced by APCs that are essential for T cell activation. In addition, the presence of another APC-derived co-stimulatory signal (Signal 3) that is responsible for controlling differentiation of T cells, has also been proposed. In vaccine development, Signals 2 and 3 have been stimulated by a diverse range of compounds known as adjuvants; members of this group include oil emulsions, surfactants, aluminum hydroxide gels, bacterial derivatives and even bread crumbs and tapioca (Pg. 849, Columns 1-2, Paragraph, spanning).
With respect to methods of enhancing immune responses by delivering peptide antigens into hosts, the state of the art at the time of filing was such that this was not possible without the presence of an adjuvant. Oxenius (Journal of Virology, Vol. 73, No. 5, Pg. 4120-4126, 1999) teaches that to achieve protective immunity when using T-cell epitopes to enhance immune responses, the use of adjuvants is normally required (Pg. 4122, Column 2, Paragraph, third full). This point is echoed by Heffernan (Biomaterials, Vol. 32, Pg. 926-932, 2011) with the teaching that adjuvants are required in order for recombinant proteins to generate immune responses in a host (Abstract).
Thus, the art does not recognize a functional immunogenic composition like those claimed comprising no adjuvant.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 295-305 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product/judicial exception without significantly more.
The claim(s) recite(s) compositions with polynucleotides that encode tumor specific T-cell epitopes from SEC31a gene. The epitopes are made from a gene of a cancer cell in a human subject (claim 298). Thus, the mutant genes that encode the recited epitopes comprise DNA (polynucleotide) encoding the same. Thus, the recited polynucleotide DNA of all claims is a natural product. From this DNA would be made mRNA to encode the epitope and so all claims reading on mRNA are equally natural. Both this DNA and mRNA are compositions of matter and found in aqueous solution in cancer cells. Thus, the compositions recited are natural products as well, containing water as carrier/excipient. Mere isolation of this solution of DNA or mRNA does not change its nature from a natural product and so the claims rejected above read on natural products discovered by Applicant. With respect to claims 299-300, the specification does not require a vaccine to have an adjuvant in all embodiments (0450) and so the statement of vaccine does not obviate this rejection. It is intended use only, given no weight, and the structures encompassed by claim 295 are examined here for patent eligibility in claims 299-300. Claim 303 and 304 simply recite lengths of the natural protein encoded by the natural mutant gene.
Thus, all claims rejected above recite natural products which are judicial exceptions.
This judicial exception is not integrated into a practical application because the claims require no additional elements that make the claimed product different from its natural counterpart such as additional structures not found in the natural context that give new properties to the natural composition above and claimed. Also, no method steps are recited in the product claims and so no particular application is required of the claimed products.
The claim(s) do not include additional elements that are sufficient to amount to significantly more than the judicial exception because all elements of the claims are found in the natural product. Furthermore, any additional element added in the future would likely be well-understood, routine, and conventional to place in a composition with a tumor-specific mutant epitope for immunization, such as artificial carriers. Paragraph 0449 of the specification makes clear that there are typical compositions/formulations for administration and thus ones known in the art. Paragraph 0446 states that combining the active ingredient with adjuvants can be done in a conventional manner using carriers, excipients, etc. and so Applicant makes clear all these are well-understood, routine, and in their own words, conventional. Paragraphs 0359 and 0378 provide prior art with such teachings. Thus, no element is present in the claims above that renders the claim significantly more/structural or functionally different than the natural product above.
Thus, the claims are patent ineligible and rejected here.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 295, 298-299, 301-302 and 305-306 are rejected under 35 U.S.C. 102a2 as being anticipated by Sahin (US2016/0125129, with priority to 05/10/2013).
Sahin teaches methods of predicting T cell epitopes such as tumor-associated neoantigens that are immunogenic (Abstract). These can be used in vaccination against a patient’s tumor (Abstract). They teach a method comprising providing a vaccine (immunogenic composition) comprising a peptide or polypeptide with modifications predicted as immunogenic or a nucleic acid encoding said polypeptide (0035-0036). Such vaccines are described by them (0037) and may comprise a pharmaceutically acceptable carrier with one or more adjuvants (0038). Their vaccine/immunogenic composition need not be prophylactic, only therapeutic (0038). For the composition above with nucleic acids, such comprises a nucleic acid delivery vehicle that targets dendritic or other antigen presenting cells, resulting in transfection that occurs in vivo (0099). Their vaccine comprises a polypeptide comprising one or more modifications predicted as immunogenic by their methods or a nucleic acid, preferably RNA, encoding said polypeptide (0208). Importantly, they define mutation to include Indels (0156) which are insertions or deletions which cause frameshift mutations (0157). Thus, one of ordinary skill in this art is taught to envision frameshift mutation at each recitation of “mutation”. With respect to specific mutations for use in their vaccine/methods, they predicted immunogenic epitopes from a human tumor model using the MZ7-MEL cell line from malignant melanoma of a patient (0294). They found at least 12 neoantigen epitopes (0295 and Table 6). Table 6 teaches these 12 mutations that result in a change of protein sequence (nonsynonymous) which were labeled as immunogenic (Table 6 legend on table) and so each therein is an immunogen taught by them useful in a vaccine of their invention. Table 6 teaches SEC31A as a gene with such an immunogenic mutation. Since mutation was used, the practitioner envisions frameshift mutations from Indels as an embodiment as discussed above. Furthermore, though the sequence of this SEC31A mutation is not given, it can be obtained from the DNA of the cell line above and so the teachings are enabling for its use in the vaccine. It is clear that one of ordinary skill in this art would envision using this mutated SEC31A gene in the taught vaccine context since both DNA and RNA are taught for such purpose (0113 and 0153) and the mRNA can and would be mRNA as the target antigen is a protein and mRNA encodes proteins (0175). The nature of the SEC31A gene mutation species they identified is not given. While the genus of frameshift mutations therein is envisioned as discussed above, the specific mutation present in the cell line is not taught. However, barring evidence to the contrary, the mutation present in the cell line meets the structural limitations of the claims above.
The office does not have the facilities and resources to provide the factual evidence needed in order to establish that SEC31A gene of the cell line above does not have a frameshift mutation and so is not included in the SEC31A mutated genus recited. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed mutations are different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Since Sahin teaches frameshift mutations/Indels are contemplated at the recitation mutation, and mutation of SEC31A is taught as an immunogen of their invention, they clearly anticipate the genera of the claims above. Furthermore, with respect to the specific structure they provide for SEC31A mutant, found in the cell line supra, the burden is on Applicant to establish it is not a frameshift mutant and so not encompassed by the instant claims.
With respect to claim 298, there is no evidence normal skin cells express this mutant of SEC31A and indeed they would not as it is classified by Sahin as immunogenic and so such cells would be seen as abnormal and removed.
Claim Rejections - Improper Markush Grouping
Claims 295-306 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, the claims above have several improper Markush groups.
First, they contain several types of composition agents to include a peptide, nucleic acid, APC that need not contain both the peptide and nucleic acid above, T cells, or a TCR. Peptides and nucleic acids are different types of biomolecules and so share no structure in common. Since this is the case, they also have different functions. The APC and T cells are cells and neither need contain the peptide or nucleic acid above and so have no structure in common therewith. The TCR is not encoded by the nucleic acid, nor does it contain the peptide. It also has different functions than both as a receptor and not a nucleic acid or ligand peptide. The APC would not have the TCR either. Taken together, none of the agents share a common structure essential to their utilities. Also, none share the same utility at all as each has a different function.
Second, the claims recite multiple genes as sources of tumor-specific neoepitopes. These genes encode different proteins and thus different epitope sequences. Therefore, they have no structure in common essential to their utility. Furthermore, it is in no way clear that they share the same utility at all, being useful for the treatment of one cancer type. For these reasons, the claims are also rejected here.
Third, even when the claims are examined focused on SEC31A, claim 297 recites various epitopes therefrom. However, not all share a common core sequence essential to their utility as MHC ligands for use in cancer treatment. T cell epitopes are generally 9 residues in length and so 9 residues would be required for MHC binding. The sequences presented do not share a 9-residue sequence or even as little as a trimer, though such would be too small to be a substantial structural feature as it alone would not provide the epitope utility. Thus, even the species list for SEC31A is an 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).
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.
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Claims 295-302 and 305-306 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 77-78, 80, and 98-100 of copending Application No. 17/599468 in view of Sahin (US2016/0125129, with priority to 05/10/2013).
Copending claim 77 recites a cell population with antigen-specific T cells and such are specific for immunogenic epitopes bound to MHC wherein the epitope sequence is a mutation expressed by cancer cells and not non-cancer cells (copending claim 78). Copending claim 80 teaches the epitope can be found in Tables 1B and 3, both of which provide SEQ ID NO. 409, which is identical to instant SEQ ID NO. 1131. Copending claim 98 is use of such a peptide in a cell population with APCs and T cells to stimulate cytotoxicity of the T cells. Thus, the copending claims render obvious a stimulatory composition that causes immune reaction against the tumor-specific epitope. Copending claim 100 makes clear a polynucleotide encoding the antigen peptide can be used for stimulation of T cells. Thus, a composition comprising a polynucleotide encoding instant SEQ ID NO. 1131 is made obvious by the copending claims and renders the claims rejected above obvious.
They do not teach use of carriers or adjvuants with such a peptide for these purposes but use of peptides in aqueous solutions with adjuvants to cause immune system reactions like T cell activation are standard practice in this art.
Also, they are taught by Sahin who teaches methods of predicting T cell epitopes such as tumor-associated neoantigens that are immunogenic (Abstract). These can be used in vaccination against a patient’s tumor (Abstract). They teach a method comprising providing a vaccine (immunogenic composition) comprising a peptide or polypeptide with modifications predicted as immunogenic or a nucleic acid encoding said polypeptide (0035-0036). Such vaccines are described by them (0037) and may comprise a pharmaceutically acceptable carrier with one or more adjuvants (0038). Their vaccine/immunogenic composition need not be prophylactic, only therapeutic (0038). For the composition above with nucleic acids, such comprises a nucleic acid delivery vehicle that targets dendritic or other antigen presenting cells, resulting in transfection that occurs in vivo (0099). Their vaccine comprises a polypeptide comprising one or more modifications predicted as immunogenic by their methods or a nucleic acid, preferably RNA, encoding said polypeptide (0208). It is clear that one of ordinary skill in this art would envision both DNA and RNA for use in the composition as Sahin teaches both for such a purpose (0113 and 0153) and the mRNA can and would be mRNA as the target antigen is a protein and mRNA encodes proteins (0175).
Thus, the combination of the copending claims and Sahin render all instant claims above obvious and they are rejected here.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/Michael Allen/Primary Examiner, Art Unit 1642