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 .
The amended claims dated 2/2/2026 are under consideration.
The amendments and arguments presented in the papers filed 2/2/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 9/2/2025 listed below have been reconsidered as indicated.
a) The amendments to the specification addressing trade name and mark usage are acknowledged.
b) Any objection and rejections of claims 114 and 148 are rendered moot in view of the cancellation of the claims.
c) The rejection of claim 116 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in view of the amendments to claim 113.
d) The rejections of: claim(s) 113-114, 116, 132, 133, 145, 147 and 149-157 under 35 U.S.C. 102(a)(2) as being anticipated by Motz 1 (US 2018/0258149 A1); and claims 113-114, 116, 132, 133, 145, 147 and 149-157 under 35 U.S.C. 102(a)(2) as being anticipated by Motz 2 (WO 2017/049166 A1), are withdrawn in view of the amendments to the claims. The Motz references do not teach an ATAC profile that may be used to select cells to be administered as Motz profiled the cells after being administered.
e) The rejections of claims 113-116 under 35 U.S.C. 103 as being unpatentable over Xu (Blood. 2014. 123(24):3750-3759) in view of Crompton (Cellular and Molecular Immunology. 2016. 13:502-513) are withdrawn in view of the amendments to the claims.
f) The rejections of: claim 146 under 35 U.S.C. 103 as being unpatentable over Motz 1 (US 2018/0258149 A1; priority date of 9/16/2016) in view of Blatti (Nucleic Acids Research. 2015. 43(8):3998-4012); and claim 146 under 35 U.S.C. 103 as being unpatentable over Motz 2 (WO 2017/049166 A1; priority date of 9/17/2015) in view of Blatti (Nucleic Acids Research. 2015. 43(8):3998-4012), are withdrawn.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Election/Restrictions
Applicant elected without traverse Group I, claims 113-116 and 132-133 and 145-157, in the reply filed on 7/2/2025.
New claims 158-160 are included with the election of Group I.
Unelected claims 117-131 and 134-144 were cancelled.
The restriction requirement between Groups I, III and IV was previously withdrawn due to a lack of burden in examining the groups together.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout 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 or cited on a submitted IDS, they have not been considered.
Claim Objections
Claim 113 is objected to because of the following informalities: the claim lacks a colon after the preamble. Appropriate correction is required.
Claim 115 is objected to because of the following informalities: the claim recites “the attribute or feature” and “the cell composition” multiple times rather than “the predetermined attribute or feature” and “the T cell composition”, respectively. Appropriate correction is required.
Claim 115 is objected to because of the following informalities: the claim lacks a colon after the phrase “wherein the attribute or feature is”. Appropriate correction is required.
Claim 116 is objected to because of the following informalities: the claim recites “the cell composition” multiple times rather than “the T cell composition”, respectively. Appropriate correction is required.
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 113, 115, 116, 132, 145, 146, 147, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159 and 160 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more.
The following are new rejections necessitated by the amendments to the claims.
The claims recite method steps and thus are processes under 35 USC 101.
The claim(s) recite(s) steps of:
“comparing the epigenetic property of the one or more genomic regions, individually, to a reference profile, wherein the comparison indicates whether the cell exhibits or is likely to exhibit a predetermined attribute or feature” (claim 113);
“if the comparison indicates that the cell composition has or is likely to have a predetermined attribute or feature” (claim 113);
“selecting the cell composition for administration to a subject” (claim 113);
“aligning, filtering and mapping the sequence reads to genomic regions of a genome” (claim 145);
“determining or identifying peaks of sequence reads in a plurality of genomic regions for each cell or population of cells” (claim 145);
“comparing peaks of sequence reads in a plurality of genomic regions for each cell or population of cells” (claim 149);
“comparing the epigenetic property of the one or more genomic regions, individually, to a reference profile, wherein the comparison indicates whether the cell exhibits or is likely to exhibit a predetermined attribute or feature” (claim 158);
“if the comparison indicates that the cell composition has or is likely to have a desired attribute or feature” (claim 158); and
“selecting the cell composition for administration to a subject” (claim 15).
The above steps of “comparing”, “selecting” and “aligning” are judicial exceptions in the form of abstract ideas in that they can be performed in a purely mental manner. The amount of information to be considered and compared broadly encompasses a single genomic region or two genomic regions. The “selecting” is based on a simple consideration of the results of the “comparing” steps.
Even though claim 145 requires a “sequencing” step, the claim encompasses sequencing “a portion” of the tagged fragments, and thus, encompasses the analysis of a sequence for a single genomic region. The sequencing depth and length of sequences is not limited in any manner.
The judicial exceptions are not integrated into a practical application because the claims do not involve:
improvements to the functioning of a computer or to any other technology or technical field;
applying or using the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition;
applying the judicial exception with, or by use of, a particular machine; or
effecting a transformation or reduction of a particular article to a different state or thing.
The claimed limitations add insignificant extra-solution activity to the judicial exceptions. The step of “performing ATAC-seq or ChIP-seq” is mere data gathering step.
While claim 116 further comprises embodiments in which administering cell compositions occurs, the administration is not required by all embodiments of the claim because option (v) is to not administer the cell composition.
Similarly, the abstract idea of “selecting” the cell composition for administration to a subject, is conditioned on whether the comparison “indicates that the cell composition has or likely to have a predetermined attribute or feature.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims encompass the use of commercially available and well-known techniques as described in paragraphs 59, 76, 124, 129, 131 and 133 of the instant specification.
Examiner’s response to the traversal of the 101 rejections
The Remarks argue claim 113 as amended recites, inter alia, performing ChIP-seq or ATAC-seq and comparing the epigenetic property of the one or more genomic regions, individually, to a reference profile, wherein the comparison indicates whether the cell exhibits or is likely to exhibit a predetermined feature or attribute, and if the comparison indicates that the cell composition has or is likely to have a desired feature or attribute, selecting the cell composition for administration to a subject. The Remarks further argue claim 113 is directed to patent eligible subject matter at least because claim 113 recites the physical steps of performing ATAC-seq or ChIP-seq and because the claim recites selecting the cell composition for administration to a subject. The Remarks further argue the claim as amended is not directed to an abstract idea, as the steps of ATAC-seq of ChIP-seq cannot be performed in a "purely mental manner." and selecting a cell composition for administration to a subject integrates the alleged exception into a practical application. See p. 9.
The arguments have been fully considered but are not persuasive. The amended claims recite judicial exceptions identified in the above rejection. The step of “performing ATAC-seq or ChIP-seq” is a data gathering step and involves routine and commercially available techniques in view of the instant specification.
The step of “selecting the cell composition for administration to a subject” is an abstract idea as noted above. The step does not require any active step of “administering” the cell composition to the subject. This is evidenced by claim 116, which encompasses “not administering the cell composition to the subject”.
It is not the examiner’s position that that method as a whole may be performed in a purely mental manner, but rather the steps specifically identified in the rejection above are abstract ideas. The additional step fails to integrate the judicial exception into a practical application as it a data gathering step.
The step of “selecting the cell composition for administration to a subject” does not integrate the method into a practical application as itself is an abstract idea and a judicial exception cannot integrate itself. MPEP 2106.04.II.A.2.
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.
Claim 149 is 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.
Regarding claim 149, the claim recites “determining the epigenomic property”. The recitation lacks proper antecedent basis in view of the amendments to claim 113, which deleted the active method step of “determining an epigenomic property”.
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 113-116, 132, 147, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159 and 160 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu (Blood. 2014. 123(24):3750-3759; cited on the 2/1/2024 IDS) in view of Araki (Immunity. 2009. 30:912-925).
The following are new rejections necessitated by the amendments to the claims.
Regarding claims 113, 115 and 116, Xu teaches “performing” a phenotype analysis of populations of CD8 T cells.
Xu teaches indicating a “predetermined attribute or feature” within the CD8+CD45RA+CCR7+ phenotype of T cells comprising a recombinant receptor (p. 3751, CD8+CD45RA+CCR7+ subset correlates with in vivo expansion of CAR-T cells infused in patients with B-cell malignancies), as a “CD8+ primary human T cell…comprising [a] recombination receptor”. Xu teaches this cell phenotype is a T-memory stem cell or naïve phenotype (Abstract; p. 3753).
Xu teaches comparing the phenotypes between different populations in “reference” to one another, i.e., one phenotype is analyzed in reference to another and vice versa.
Xu teaches the phenotype is indicative of an outcome of the persistence of the cells which is the basis for the durability of an anti-tumor response and the phenotype indicates expansion of the CAR-T cells in the first 6 weeks after infusion and administering the cells to a subject (p. 3751, CD8+CD45RA+CCR7+ subset correlates with in vivo expansion of CAR-T cells infused in patients with B-cell malignancies).
Alternatively, Xu teaches the attribute or feature is the phenotype and function of the cells (p. 3751, CD8+CD45RA+CCR7+ subset correlates with in vivo expansion of CAR-T cells infused in patients with B-cell malignancies).
It would have been prima facie obvious to use the CD8+CD45RA+CCR7+ phenotype for selection of a T cell composition for administering to a subject because they persist after treatment and indicates expansion of the CAR-T cells after infusion as described by Xu. It would have been prima facie obvious to have administered the CD8+CD45RA+CCR7+ T cell composition to treat the patient.
Regarding claim 114, Xu teaches comparing phenotypes and outcomes between different groups, with groups serving as references for one another.
Regarding claims 150-152, as noted above, Xu teaches the T cell composition is genetically engineered to carry a CAR.
Regarding claim 153, Xu teaches the T cell composition comprises greater than 70% of primary CD8 T cells that are not CCR7+ and CD45RA+ (Figure 2).
Regarding claims 154-157, the claims further limit element (i) of claim 116. The claim still encompasses administering the T cell composition indicated as having the CD8+CD45RA+CCR7+ phenotype. It is this embodiment that is rendered obvious by Xu.
Regarding claims 154 and 155, Xu teaches altering a condition in engineering the cells of the T cell composition by exposing them to IL-7 and IL-15 for 12 to 14 days (p. 3751, Cell lines and CAR-T cell generation).
Regarding claims 158 and 160, Xu teaches generating an engineered T cell composition by transducing CD8 T cells to express a CAR (p. 3751, Cell lines and CAR-T cell generation)
Xu teaches “performing” a phenotype of populations of CD8 T cells.
Xu teaches comparing the phenotypes between populations in “reference” to one another.
Xu teaches indicating a “predetermined attribute or feature” within the CD8+CD45RA+CCR7+ phenotype of T cells comprising a recombinant receptor (p. 3751, CD8+CD45RA+CCR7+ subset correlates with in vivo expansion of CAR-T cells infused in patients with B-cell malignancies).
Xu teaches the phenotype is indicative of an outcome of the persistence of the cells which is the basis for the durability of an anti-tumor response and the phenotype indicates expansion of the CAR-T cells in the first 6 weeks after infusion and administering the cells to a subject (p. 3751, CD8+CD45RA+CCR7+ subset correlates with in vivo expansion of CAR-T cells infused in patients with B-cell malignancies).
Alternatively, Xu teaches the attribute or feature is the phenotype and function of the cells (p. 3751, CD8+CD45RA+CCR7+ subset correlates with in vivo expansion of CAR-T cells infused in patients with B-cell malignancies).
It would have been prima facie obvious to use the CD8+CD45RA+CCR7+ phenotype for the selection of a T cell composition for administering to a subject because they persist after treatment and indicates expansion of the CAR-T cells after infusion as described by Xu. It would have been prima facie obvious to have administered the CD8+CD45RA+CCR7+ T cell composition to treat the patient.
Regarding claim 159, Xu teaches the phenotype is indicative of an outcome of the persistence of the cells which is the basis for the durability of an anti-tumor response (p. 3751, CD8+CD45RA+CCR7+ subset correlates with in vivo expansion of CAR-T cells infused in patients with B-cell malignancies).
While Xu teaches the above methods, Xu does not teach determining an epigenetic property of the CD8+CD45RA+CCR7+ cells.
However, Araki teaches an epigenetic property of CD8 T cell phenotypes.
Regarding claims 113 and 158, Araki teaches using ChIP-Seq to analyze an epigenetic property of naïve CD8 T cells, which can be differentiated from central and effector memory CD8 T cells based on the results (Figure 2, 3 and 4).
Regarding claim 132, the method of Araki analyzes “chromatin accessibility” and/or “nucleosome occupancy”.
Regarding claim 147, Araki teaches multiple genomic regions of interest, such as SYT3 and KLRG1 (Figure 4).
Regarding claim 149, Araki teaches comparing sequencing peaks between CD8 T cell phenotypes (p. 921, Analysis of ChIP-Seq Data; and Figure 3).
It would have been prima facie obvious to the ordinary artisan to have use the epigenetic analysis of Araki in place of the phenotype analysis of Xu because it provides more information and generates a comprehensive picture of cell status such that selection may be better fine-tuned for those cells that are beneficial after transfer.
Claims 145 and 146 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu (Blood. 2014. 123(24):3750-3759; cited on the 2/1/2024 IDS) in view of Araki (Immunity. 2009. 30:912-925) and in further view of Buenrostro (Current Protocols in Molecular Biology. 2015. 21.29.1-21.29.9).
The following are new rejections necessitated by the amendments to the claims.
Regarding claims 145 and 146, the combination of Xu and Araki renders obvious the elements of claim 113 as required by claims 145 and 146.
The combination does not teach the additional elements specific to claims 145 and 146.
However, Buenrostro teaches ATAC-seq was a known technique (p. 21.29.1). Buenrostro teaches methods such as ChIP-seq, require hundreds of millions of cells as input material, averaging out heterogeneity in cellular populations (p. 21.29.1-21.29.2), while ATAC-seq uses 50,000 cells (p. 21.29.2). ATAC-seq involves the analysis of >50,000,000 or >200,000,000 mapped reads, depending on the analysis (p. 21.29.7). ATAC-seq determines fragments size per mapped reads (Fig. 21.29.2).
It would have been prima facie obvious to the ordinary artisan to have replaced the ChIP-seq of Araki with the ATAC-seq of Buenrostro to arrive at the method of claims 145 and 146. One would have been motivated to do so because ATAC-seq requires less cellular input for the analysis.
Conclusion
No claims allowed.
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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.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682
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