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 1-3, 6-9, 25-30, 57-58, 67, 138-139, 141, and 282, of record 2/26/2026, are pending and subject to prosecution. Claims 1 and 138 are amended.
Status of Prior Objections/Rejections
RE: Objection to the specification:
The amendment to the specification is effective to obviate the objection. The objection is withdrawn.
RE: Objection to claim 138:
The amendment to claim 138 is effective to obviate the objection. The objection is withdrawn.
RE: Rejection of claim 67 under 35 U.S.C. 101:
The amendment to claim 67 is not effective to overcome the rejection. As previously stated, the claimed T cell population is described using product-by-process language, which does not impose any structural or functional attributes differentiating it from naturally-occurring T cell populations. T cells specific for one or more of the enumerated SEQ ID NOs are found in nature (See rejections below).
The rejection is maintained in modified form to address amended limitations.
RE: Rejection of claims 67, 138-139, and 282 under 35 U.S.C. 102(a)(1) over Szmania et al. (Blood, 2001):
RE: Rejection of claim 67 under 35 U.S.C. 102(a)(1) and 102(a)(2) over Langer (WO 2020205662 A1):
RE: Rejection of claims 1-3, 6-8, 25-30, and 67 under 35 U.S.C. 103 over Langer (WO 2020205662 A1) in view of Perica et al. (ACS Nano, 2015):
RE: Rejection of claims 1-3, 6-9, 25-30, and 67 under 35 U.S.C. 103 over Langer (WO 2020205662 A1) in view of Perica et al. (ACS Nano, 2015), further in view of Scheffel et al. (Cancer Immunology, Immunotherapy, 2016):
RE: Rejection of claims 1-3, 6-8, 25-30, 57-58, and 67 under 35 U.S.C. 103 over Langer (WO 2020205662 A1) in view of Perica et al. (ACS Nano, 2015), further in view of Torikai et al. (Blood, 2013):
RE: Rejection of claims 67, 138-139, 141, and 282 under 35 U.S.C. 103 over Szmania et al. (Blood, 2001):
The amendment to claims 1 and 138 is effective to obviate the rejections. The rejections are withdrawn.
New/Maintained Rejections
Claim Interpretation
Claim 67 recites a “population of antigen-specific T cells made by the method of claim 1”. The cells of the population are defined using product-by-process limitations. Product-by-process limitations are considered only in so far as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product as claimed is the same or obvious over a product of the prior art (i.e., is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113. In the instant application, because the method of claim 1 does not distinguish the T cells structurally from antigen-specific T cells generated by other methods, the cells are interpreted as comprising any antigen-specific T cells, wherein one or more of the T cells is specific for at least one of SEQ ID NOs 1-56, 59-69, and 74-79.
Claim Rejections - 35 USC § 112
Claims 1-3, 6-9, 25-30, 57-58, 67, 138-139, 141, and 282 are rejected on the 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). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP 2117.
The Markush grouping recited in claims 1 and 138 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The peptides do not share significant overall sequence similarity (See identity matrix below). SEQ ID NOs 1, 10, 20, 30, 40, 50, 60, and 74 were arbitrarily selected for alignment. Additionally, the peptides are derived from different proteins from different viruses and would thus generate very different populations of antigen-specific T cells (i.e., no common use).
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To overcome this rejection, the applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim 67 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
The claim has been analyzed for eligibility in accordance with its broadest reasonable interpretation.
Regarding claim 67: The claim is directed to a population of antigen-specific T cells made by the method of claim 1. The broadest reasonable interpretation of the resulting cells is considered to cover naturally occurring antigen-specific T cells, wherein one or more of the T cells is specific for at least one of SEQ ID NOs 1-56, 59-69, and 74-79. Based upon this interpretation, the claims are analyzed as follows:
Step 1: The claim is to a composition of matter, which is a statutory category of invention (Step 1: YES).
Step 2A, prong 1: The claimed cells are described using product-by-process language, which is considered for the markedly different characteristics analysis. T cells, including antigen-specific T cells, are nature-based products. When a claimed composition includes a nature-based product, further analysis is taken to determine if the claimed composition recites a nature-based product judicial exception by comparing the claimed composition to the closest naturally occurring counterpart to determine if the claimed composition has markedly different characteristics than the counterpart.
The closest naturally occurring counterpart of T cells are naturally occurring T cells, which may be antigen-specific. For instance, Kelvin et al. teach antigen-specific T cells isolated from SARS-CoV patients, including cells that are specific for a peptide antigen identical to instant SEQ ID NO 76 (See page 60, line 1-15; table 3, SEQ ID NO 303). There is no evidence that the cells as claimed differ from T cells in nature in terms of structural or functional characteristics. The claimed composition therefore does not have markedly different characteristics from what occurs in nature and is a "product of nature" exception. Accordingly, the claim is directed to an exception (Step 2A, prong 1: YES).
Step 2A, prong 2: The claim is directed to a product and do not recite any structure that serves to integrate the composition into a practical application (Step 2A, prong 2: NO).
Step 2B: There are no additional elements required by the claim. The claim does not qualify as eligible subject matter and is properly rejected under 35 U.S.C. 101.
Claim Rejections - 35 USC § 102
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 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 67 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Kelvin et al. (WO 2005103259 A1).
Regarding claim 67: Kelvin et al. teach immunodominant SARS-CoV nucleocapsid epitopes (which read on “microbial peptides” and “viral… peptides”) for use in treating and preventing infection (See Abstract and page 22, line 9-17). Kelvin et al. teach T cells activated by (which reads on “antigen-specific”) the peptide LLLDRLNQL, which is identical to instant SEQ ID NO 76, from SARS-CoV patients (See page 60, line 1-15; table 3, SEQ ID NO 303; and alignment below).
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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.
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 138-139, 141, and 282 are rejected under 35 U.S.C. 103 as being unpatentable over Langer (WO 2020205662 A1), of record, in view of Kelvin et al. (WO 2005103259 A1).
Regarding claims 138-139, 141, and 282: Langer teaches methods for the ex vivo expansion of T cells by stimulations with APCs (See Abstract and ¶0106). CD4+ and/or CD8+ T cells are enriched or selected (which reads on “isolating”) from a biological sample (See ¶0195). The T cells are co-cultured with APCs loaded with a peptide or plurality of different peptides (See ¶0106 and 0194). The T cells can be incubated with one or more cytokines (which reads on “a plurality”), such as IL-2, IL-7, and IL-15, during co-culturing with APCs (See ¶0033-0034, 0097). The T cells and APCs can be autologous and isolated from a biological sample (which reads on “a sample”) (See ¶0052, 0063-0065, 0344). The APCs can be dendritic cells (See ¶0075, 0194, and 0342). The APCs can also be artificial APCs (See ¶0353). The APCs can express MHC class I and/or class II molecules including HLA-A, HLA-B, HLA-C, HLA-DP, HLA-DQ, HLA-DM, HLA-DR, or HLA-DO for peptide presentation (See ¶0342-0343). Langer does not expressly teach specific viral antigenic peptides.
Kelvin et al. teach immunodominant SARS-CoV nucleocapsid epitopes (which read on “microbial peptides” and “viral… peptides”) for use in treating and preventing infection (See Abstract and page 22, line 9-17). The peptide epitopes are capable of eliciting T cell induction, activation, proliferation, or lytic activity and can be used in multimers with MHC molecules (See page 22, line 18-31; page 24, line 19-34; and page 25, line 1-4). Kelvin et al. teach the peptide LLLDRLNQL, which is identical to instant SEQ ID NO 76, as an HLA A2-binding peptide eliciting CD8 T cell proliferation and reactivity in patients (See page 60, line 1-15; table 3, SEQ ID NO 303; and alignment below).
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It also would have been obvious to further modify the method of Langer to comprise SARS-CoV peptides taught by Kelvin et al., including LLLDRLNQL (such peptides would read on “a first exogenous peptide” and “a second exogenous peptide”). One would have been motivated to make this modification because Kelvin et al. teach that the peptide is one of multiple epitopes that are HLA-binding and able to induce T cell proliferation and reactivity in SARS-CoV patients (See page 60, line 1-15), and thus could be used to expand SARS-CoV-specific T cells. There would be a reasonable expectation of success in doing so because the peptides taught by Kelvin et al. could be readily used in the method of Langer and because Langer teaches that the resulting T cells can be used to target virally-infected cells (See ¶0177 and 0490).
Claims 1-3, 6-8, 25-30, 67, 138-139, 141, and 282 are rejected under 35 U.S.C. 103 as being unpatentable over Langer (WO 2020205662 A1), of record, in view of Kelvin et al. (WO 2005103259 A1), further in view of Perica et al. (ACS Nano, 2015), of record.
Regarding claims 1-2, 6-8, 25-30, and 67: Following the discussion of claims 138-139, 141, and 282, Langer, modified by Kelvin et al., render obvious a method for generating viral antigen-specific T cells but do not teach the artificial APCs as comprising a peptide-binding HLA and CD28-binding protein bound to a solid support.
Perica et al. teach an artificial APC comprising a nanoparticle (which reads on “solid support”) bearing a chimeric MHC-Ig dimer and an anti-CD28 antibody (which reads on “protein that specifically binds to CD28”) (See fig. 1). The nanoparticles can also be functionalized with human HLA-A2 (which reads on “peptide binding domain of a human leukocyte antigen… protein” and “HLA class I protein”) See page 6867, col. 1, full ¶3). The nanoparticles are loaded with neoantigenic peptides (See page 6868, col. 1, full ¶5 and col. 2, full ¶4).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Langer, modified by Kelvin et al., to incorporate the nanoparticles of Perica et al. for presenting antiviral peptides for T cell expansion. Combining prior art elements according to known methods to yield predictable results is considered to be prima facie obvious. See MPEP 2143. Each element—dendritic cells, peptides, and APC-mimicking nanoparticles—had been known to effectively expand antigen-specific T cells and, if combined, would perform the same functions that each performs separately and predictably.
Regarding claim 3: Following the discussion of claims 1-2, 6-8, 25-30, 67, 138-139, 141, and 282, Langer and Kelvin et al. do not expressly teach the T cells as effector or memory T cells. However, Langer teaches that cytokine concentrations can be modified to drive T cell differentiation to a memory phenotype (See ¶0191, 0317-0318, and 0321). One would be motivated to make this modification because Langer teaches that early memory T cells may be more desirable in a therapeutic composition (See ¶0191). There would be a reasonable expectation of success in doing so because cytokine concentrations could be readily modified to yield memory or effector phenotypes.
Claims 1-3, 6-9, 25-30, 67, 138-139, 141, and 282 are rejected under 35 U.S.C. 103 as being unpatentable over Langer (WO 2020205662 A1), of record, in view of Kelvin et al. (WO 2005103259 A1), further in view of Perica et al. (ACS Nano, 2015), of record, and further in view of Scheffel et al. (Cancer Immunology, Immunotherapy, 2016), of record.
The teachings of Langer, Kelvin et al., and Perica et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claim 9: Following the discussion of claims 1-3, 6-8, 25-30, 67, 138-139, 141, and 282, Langer, modified by Kelvin et al. and Perica et al., renders obvious a method of producing antigen-specific T cells but does not expressly teach culturing the T cells with N-acetylcysteine.
Scheffel et al. teach that culturing T cells in the presence of N-acetylcysteine during in vitro expansion decreased activation-induced cell death and increased tumor control and survival in a mouse model (See Abstract and fig. 1-3).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Langer, modified by Kelvin et al. and Perica et al., to comprise the addition of N-acetylcysteine for culturing the T cells during expansion. One would be motivated to make this modification because Scheffel et al. teach N-acetylcysteine as a beneficial additive (See fig. 1-3). There would be a reasonable expectation of success in doing so because N-acetylcysteine could be readily added to the culture medium.
Claims 1-3, 6-8, 25-30, 57-58, 67, 138-139, 141, and 282 are rejected under 35 U.S.C. 103 as being unpatentable over Langer (WO 2020205662 A1), of record, in view of Kelvin et al. (WO 2005103259 A1), further in view of Perica et al. (ACS Nano, 2015), of record, further in view of Torikai et al. (Blood, 2013), of record.
The teachings of Langer, Kelvin et al., and Perica et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claims 57-58: Following the discussion of claims 1-3, 6-8, 25-30, 67, 138-139, 141, and 282, Langer, modified by Kelvin et al. and Perica et al., renders obvious a method of producing antigen-specific T cells but does not expressly teach disruption of an HLA gene in the T cells.
Torikai et al. teach the elimination of HLA expression for generating allogeneic cells for therapy (See Abstract; page 1341, col. 2, full ¶1; and page 1342, col. 1, ¶1). Zinc finger nucleases were used for editing the HLA locus in T cells (See fig. 3-5).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Langer, modified by Kelvin et al. and Perica et al., to comprise HLA gene editing, as taught by Torikai et al. One would be motivated to make this modification because Torikai et al. teach that elimination of HLA expression yields allogeneic cells that reduce allograft rejection and immune recognition of auto-antigens (See Abstract and page 1347, col. 2, ¶1-2). There would be a reasonable expectation of success in making this modification because Torikai et al. demonstrate that the zinc finger nucleases can be used in T cells to knock out expression of HLA (See fig. 3-5).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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