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 .
Claims 1-22 are under consideration.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4 and 15 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 4 recites an alternative to step b of claim 1. Claim 15 recites an alternative to step b of claim 12. These attempts to add an alternative that is not present in the base claims results in broader claims.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. This rejection could be overcome by amending claims 1 and 12 to include the desired alternative.
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.
Claims 10, 11, 21, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al., Journal of Clinical Investigation, May 2019, Vol.129, No.5, pp.2056-2070 (‘Chen’; of record).
The claims are drawn to methods of treating cancer by administering neoepitope reactive T cells. The claims recite the methods of claim 1 or claim 12 as the processes by which the therapeutic T cells are produced. Chen likewise teaches a method of treating cancer by administering neoepitope reactive T cells (Abstract; paragraph bridging pp.2061-2962). The T cell product employed in Chen is indistinguishable from that of the instant claims despite the fact that Chen does not disclose the exact method of claim 1 or claim 12. In Chen, the T cells are selected for reactivity against individual neoepitopes (Fig. 1). Steps e-g of pending claims 1 and 12 likewise select T cells for reactivity against individual neoepitopes. Both cell populations are neoepitope reactive T cells, without any further distinguishing features. Therefore, the methods of claims are anticipated by Chen, as Chen teaches treating the same patients with the same cells.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-22 are rejected under 35 U.S.C. 103 as being unpatentable over Chen as applied to claims 10, 11, 21, and 22 above, and further in view of US 20060224329 (Roth; of record), US 20200282037 (Niazi), WO 2020023713 (Soon-Shiong; of record), Kato et al., Oncotarget. 2018 Jan 13;9(13):11009-11019 (Kato).
As noted above, Chen teaches a method of treating cancer by administering neoepitope reactive T cells. In Chen, peptides comprising tumor epitopes were used to stimulate patient PBMCs, which comprise antigen-presenting cells and T cells. Neoantigen-reactive T cells were expanded and administered for personalized therapy targeting a single neoepitope (paragraph bridging pp.2061-2962). In view of Chen, one of skill in the art would expect that neoepitope reactive T cells, once identified, can be expanded and successfully used for therapeutic purposes.
The method of identifying neoantigen-reactive T cells in Chen differs from that of the present claims, as the neoantigen peptides were individually synthesized, not expressed as a polytope polypeptide in E. coli, or obtained by in vitro transcription and translation, as in step b of claims 1, 4, 12, and 15. Furthermore, Chen does not teach two steps of selection; a first identification and expansion of T cells reactive to a polytope, followed by selection of the expended T cells for recognition of individual peptides on an array, as recited in the pending claims.
Niazi teaches expressing patient-specific tumor antigens as polytopes (Abstract; [0013]). Niazi teaches that E. coli expressing neoepitopes may be used as a screen to determine whether a patient has existing immunity against the expressed neoepitopes. Such screen can be simply performed by adding the genetically modified bacteria to dendritic cells (APC) of the patient, or to HLA-matched dendritic calls. These cells are then further combined with T cells from the same patient (e.g., isolated from peripheral blood or tumor infiltrating lymphocytes), and an immune response by the T cells is then measured [0075][0077].
Soon-Shiong teaches a method of expanding antigen-reactive T cells by exposing autologous dendritic cells to a tumor antigen, coculturing the dendritic cells with T cells, enriching the activated T cells using density gradient [00132] and expanding the reactive T cells in an activation culture comprising interleukins 7, 15, and 21 (claims 24-29). The expanded T cells may then be administered to the donor (claim 30). Soon-Shiong thus complements Niazi and Chen by teaching the method of expanding antigen-specific T cells for clinical application. Together, Niazi and Soon-Shiong teach identifying neoepitopes, selection, expansion, and administration of reactive T cells as in steps a-d of claims 1, 2, 8-12. Niazi (FIG.12) and Soon-Shiong (claim 26) teach confirming the specificity and activity of neoepitope-reactive T cells by ELISPOT assay, as in step g of claims 1 and 12 and in pending claims 7 and 18).
Roth teaches a method of detecting antigen specific T cell responses to individual epitopes by transfecting one gene per well into 96-well plates containing antigen-presenting cells followed by addition of T cells from patient suspected of having T cells responsive to one or more antigens (Figure 7). The instant specification teaches “wells of a microplate” as an example of an array in the claimed methods ([0057] in publication US 20240027462). Therefore, the procedure in Roth is essentially the same as steps e-f of claims 1 and 12, the difference being that in Roth, the antigens are from a pathogenic organism, not cancer neoepitopes. One of skill in the art would expect that the utility of the array method taught in Roth wound not be limited to a single class of antigens, but rather would be generally applicable to many peptide antigens, including cancer neoepitopes. Roth also illustrates in vitro transcription and translation of desired sequences for the preparation of antigens (Fig. 2).
Kato teaches the use of a peptide-MHC-dextramer to identify neoantigen-reactive T cells (Fig. 2A), as in pending claims 6 and 17.
In summary, methods of identifying and expanding neoepitope reactive T cells, and methods of therapeutic therapeutically administering the expanded cells, were well known in the art prior to the date of the instant application. Steps a-g of claims independent claims 1 and 12 represent the sequential performance of steps known in the prior art for the purpose of identifying, expanding, and confirming the specificity and activity of neoepitope reactive T cells: first stimulating a mixed population of T cells reactive to the several epitopes in a polytope (Niazi), followed by expansion and enrichment of the stimulated T cells (Soon-Shiong), followed by selection of the expended T cells for recognition of individual peptides on an array (Roth). Specific methods of confirming the specificity and activity of neoantigen-reactive T cells, as in claims 6, 7, 17 and 18 were likewise known in the art prior to the filing of the instant application (Niazi, Soon-Shiong, Kato). Each element of the pending claims performs the function that would be expected in view of the prior art. “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398 at, 82 USPQ2d at 1395.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL C GAMETT, Ph.D., whose telephone number is (571)272-1853. The examiner can normally be reached on M-W 9:00 am-5:30pm, EST. Please note the examiner’s part-time schedule. 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.
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/DANIEL C GAMETT/Primary Examiner
Art Unit 1647