DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's preliminary amendment filed on 12/27/2023 is acknowledged.
Claims 1, 2, 4, 7-8, 11, 15, 25, 36, 44-45, 50-52, 58-59, and 62-65 are pending.
3. Claim 59 is objected to because of apparent typographical errors in the word “intracistemally,” where it appears that “intracisternally” was intended, and in the word “parenthetically,” where it appears that “parenterally” was intended. Appropriate corrections or clarifications are required.
4. 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.
5. Claims 4, 7-8, 25 and 58 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 4 is indefinite in the recitation of the method step of administering IL-7 “after a peak expansion phase of the tumor-specific T cell immune response,” because the timing of IL-7 administration is not sufficiently defined. In order for a person of skill in the art to be apprised of the timing of the “peak,” the claim should contain a recitation of either (a) a specific time frame applicable to human cancer patients, or (b) an additional method step specifying the procedure to be employed to determine the timing of the “peak” experimentally for each human patient.
The specification (Example 1 at p. 81-83 and Fig. 1) describes experiments in a mouse model system wherein IL-7 was administered either on day 4 or day 13 after the first DNA vaccine administration, with day 4 labeled as being within the “expansion phase of the tumor-specific T cell immune response” and day 13 labeled the “contraction phase.” The specification also discloses at p. 6 that “in some aspects,” the peak expansion phase of the tumor-specific T cell immune response occurs from about 7 days to about 15 days after an initial administration of the cytokine vaccine. This disclosure does not cure the deficiency of the claim, because (a) it is not a limiting definition, (b) it is unclear whether it applies to human or mouse, and (c) it is improper to import claim limitations from the specification. See MPEP 2111.01(II).
(ii) Claim 7 is indefinite in the recitation of a method of “reducing the occurrence of a tumor in a subject,” because it is unclear how the “reduction” is ascertained. Specifically, it is unknown what exactly is being reduced (e.g. the size of the tumor, the number of metastases, the time of tumor occurrence, etc.), or the standard to which the respective values are compared to determine whether or not they are “reduced.”
(iii) Claim 25 is indefinite in the recitation of “epitopes” selected from “Lrrc27, Plekho1, Pttg1, Xpo4, Exoc4, Pank3, Tmem101, Map3k6, Met, BC057079, Histlh3e, Prkag1, Neil3,” because the recited abbreviations identify human genes and the encoded proteins. As a skilled artisan would be aware, a protein may have multiple epitopes, and therefore the identity of epitopes within the scope of the claim is unknown
(iv) Claim 58 is indefinite in the recitation of “an amino acid sequence having a sequence identity of at least about 70% to SEQ ID NOs: 1-6 and 15-25,” because it is unclear whether the sequence has identity to any one of the recited SEQ ID Numbers or to all of the recited SEQ ID Numbers. The Office recommends the use of the phrase "selected from the group consisting of ..." with the use of the conjunction "and" in listing the species. See MPEP 803.02.
(v) Claim 8 is indefinite, because it encompasses the indefinite limitations of the claim on which it depends.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
6. The following is a quotation 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.
7. Claims 7-8 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not provide a sufficient enabling description of a method of “preventing” or “reducing the occurrence” of a tumor in a subject.
The specification does not enable one of skill in the art to make and use the invention as claimed without undue experimentation. Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized in In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, limited working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
The claims are directed to a method of “preventing” or “reducing the occurrence” of a tumor, which involves identifying healthy human subjects susceptible the tumor development, applying the treatment, and, after a sufficiently long period of time has elapsed, ascertaining that the absence or “reduction” of tumor occurrence in the subjects is due to the treatment and not some other factors. Therefore, the burden of enabling a method of preventing a disease is much greater than that of enabling a method of treating a disease, due to the inherent difficulty of identifying healthy human subjects susceptible the disease, and especially the hurdle of proving that the administered treatment was the factor that resulted in prevention of the disease.
The specification at describes a working example (Example 7, p. 86-87) wherein naive mice were immunized with a DNA vaccine encoding specific neoantigens, followed by administration of IL-7. 27 days post initial DNA vaccine administration the mice were implanted with tumor cells expressing the same neoantigens against which they were immunized. In the treated animals nearly no tumor growth was observed, in contrast to the control animals (Fig. 6B). These results indicate that the procedure resulted in almost complete prevention of tumor growth in this experimental system under the conditions used.
A person of skill in the art would readily appreciate that these experimental results cannot be extrapolated to spontaneous human tumors. One of the reasons for this is that the identity of neoantigens expressed by a particular tumor is unknown until the tumor has developed.
A skilled artisan would also be aware that the only effective approaches to cancer prevention known in the art are those based on lifestyle changes (see e.g. Balducci, 2016). “Although a number of agents are available for the chemoprevention of breast and prostate cancer, so far none of them has yielded a reduction of cancer-related death.” (Id., p. 321).
Accordingly, the entire scope of experimentation required to develop methods of preventing cancer by the claimed method is left to those skilled in the art, the present claims and disclosure amounting to nothing more than an invitation to the skilled artisan to invent such methods. Given the resource-intensive nature of the required experimentation, the risks involved and the extremely low expectation of success, the skilled artisan would reasonably conclude that such experimentation would be unnecessarily, and improperly, extensive and undue.
8. 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.
9. Claims 1-2, 4, 11, 15, 45, 50-52, 58-59, and 62-65 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Sahin et al. (US 20210113606).
Sahin teaches a method of treating cancer comprising administering RNA encoding a tumor-associated antigen or epitope and IL-7, wherein IL-7 is administered intravenously as a nucleic acid encoding the IL-7 protein (e.g. claim 21), and wherein IL-7 is a fusion with a half-life extending moiety such as albumin or Fc fragment (e.g. claims 5 and 7).
Sahin described working examples of the treatment in mouse models, wherein IL-7 was administered 2 days after RNA vaccination (e.g. [0354]), and exemplifies multiple useful tumor antigens from various cancers (e.g. [0248]), including HER2 and most other antigens recited in instant claim 62.
In cytokines and fusion proteins utilized by Sahin, the “coding sequences originate from Mus musculus and no changes in the resulting amino acid sequences were introduced” [0348]. In particular, the sequence of mIL7 is defined by RefSeq “NP_032397.1” (Id), which is identified as “P10168” in UniProt database and is 100% identical to instant SEQ ID NO:3 (see SCORE). Sahin teaches constructs both with and without the signal peptide (e.g. [0348]).
Accordingly, Sahin’s method is within the scope of instant claims 1-2, 11, 45, 50-52, 58-59, and 62-65, and as such anticipates these claims.
Claim 4 is included in the rejection because, while the timing of “peak expansion” is unknown (see subsection 4(i) above). Claim 15 is included in the rejection because, since Sahin’s method is the same as instantly claimed, the outcomes of practicing the method are inherently the same.
10. Claims 1-2, 4, 11, 15, 36, 44-45, 50-52, 59 and 64 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Choi et al. (2016; including “Supplementary materials and methods”).
Choi describes treating cervicovaginal cancer in a mouse model by administering DNA vaccine encoding HPV tumor antigen followed by administration of IL7-Fc fusion protein (e.g. the Abstract) 7 days after the first vaccination (p. 5902).
IL7-Fc was administered at a dose of 10 μg to female C57BL/6 mice 8 to 10 weeks of age (p. 5899 and Supplementary materials and methods). Assuming animal body weight of 20 grams, the dose equals 500 μg/kg, which is within the scope of instant claim 36. Choi also describes weekly administration of IL7-Fc at doses of 0.8, 3 and 8 mg/kg (p. 5902 and Supplementary materials and methods).
Claim 4 is included in the rejection because, while the timing of “peak expansion” is unknown (see subsection 4(i) above), the specification discloses at p. 6 that “in some aspects” the peak may occur at “about 7 days,” i.e. administration at 7 days is deemed to occur after “about 7 days.” Claim 64 is included, because the IL7-Fc was produced by expression in CHO cells (p. 5899) which are assumed to have removed the signal peptide.
11. 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 of this title, 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.
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.
12. Claims 1 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Sahin et al. (US 20210113606) in view of Lai et al. (US 20050020520).
Claim 25 lists tumor antigens derived from breast cancer.
Sahin teaches the method of instant claim 1 (see section 9 above) and exemplifies multiple useful tumor antigens from various cancers (e.g. [0248]).
Although Sahin does not specifically exemplify the antigens listed in instant claim 25, these antigens were known to be useful as components of cancer vaccines. For example, Lai teaches and claims a DNA vaccine encoding the Met oncogene.
The combined teachings of Sahin and Lai would have provided both the motivation and the expectation of success in using DNA vaccine encoding the Met oncogene in the method taught by Sahin.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
13. Conclusion: no claim is allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 8:30 AM – 5 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel Kolker can be reached at 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644