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 7/2/2025 are under consideration.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 113-116 and 132-133, in the reply filed on 7/2/2025 is acknowledged.
New claims 145-157 depend from claim 113 and are included with the election of Group I.
Unelected claims 117-131 and 134-144 have been cancelled.
The restriction requirement between Groups I, III and IV is withdrawn.
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Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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.
Specification
The use of terms, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. It is noted that in the term DYNABEADS® is properly identified, but CliniMACS® Prodigy® is not properly identified.
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 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 113-116, 132-133 and 145-157 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more.
The claims recite method steps and thus are processes under 35 USC 101.
The claim(s) recite(s) steps of:
“analyzing or determining an epigenetic property of one or more genomic regions of a T cell composition” (claim 113);
“comparing the epigenetic property for each of the one or more genomic region, individually, to the corresponding epigenetic property from a reference profile” (claim 114);
“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); and
“comparing peaks of sequence reads in a plurality of genomic regions for each cell or population of cells” (claim 149).
The above steps 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.
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. 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.
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.
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 116 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 116, the claim recites “the comparison” in line 4. The recitation lacks proper antecedent basis and the claim is incomplete because no step of “comparing” is required nor is a step of “providing” or “obtaining” a comparison.
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 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(s) 113-114, 116, 132, 133, 145, 147 and 149-157 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Motz 1 (US 2018/0258149 A1; priority date of 9/16/2016).
Claims 113-114, 116, 132, 133, 145, 147 and 149-157 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Motz 2 (WO 2017/049166 A1; priority date of 9/17/2015).
The Motz 1 reference is a 371 national stage application of PCT/US2016/052260, which is the basis for the Motz 2 reference. The two references are deemed to have the same disclosure based on their continuity relationship. Citations in the following rejections are to the Motz 1 reference.
Regarding claims 113, 132 and 133, Motz teaches determining an epigenetic property of genomic regions of a population of cells comprising a recombinant receptor by performing Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) to determine chromatin accessibility on enriched chimeric antigen receptor (CAR) positive CD8+ T cells (para. 1027).
Regarding claim 114, Motz teaches comparing the epigenetic property for genomic regions between two populations, with one being a reference for the other (para. 1027). One population was less differentiated (para. 1027), meaning the other was more differentiated and is indicative of less persistence to provide robust and long-term anti-tumor activity as a feature or attribute.
Regarding claim 115, Motz teaches the attribute or feature is a phenotype or function of the cells as noted above.
Regarding claim 116, Motz teaches the attribute is an outcome in the form of persisting to provide robust and long-term anti-tumor activity as noted above and administering the cells to a subject (para. 1027).
Regarding claim 145, Motz teaches Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) as noted above. An ATAC-seq process includes the steps of claim 145.
Regarding claim 147, the phrase “a panel that includes at least 2 to 50 genomic regions” is interpreted as being any number of genomic regions that is 2 or more. This is based on the use of the term “includes”, which is interpreted “comprising”, and the phrase “at least” being applied to any number between 2 and 50, inclusive.
Motz teaches using ATAC-seq in which DNA fragments get incorporated into regions of open chromatin, which allow for determination of which chromatin regions are opened versus closed (para. 1027), which encompasses at least two open chromatin regions.
Regarding claim 149, Motz teaches comparing peaks of sequencing reads and identifying peaks of sequence reads that are different between samples from two or more cell compositions (para. 1027).
Regarding claims 150, 151 and 152, Motz teaches the cell has a chimeric antigen receptor (para. 1027), resulting from genetic engineering.
Regarding claim 153, Motz teaches the target cells are 100% CD3+ T cell (para. 620).
Regarding claim 154, the claim further limits alternative (i) of claim 116, which is under the embodiment “if the comparison indicates that the cell composition is not or is not likely to exhibit the outcome”. Claim 154 is not limited to performing alternative (i), but also encompasses “administering the cell composition to the subject” because “the comparison indicates that the cell composition is or is likely to exhibit the outcome”. Motz anticipates that embodiment of claim 154 in which the cell composition is administered.
Regarding claims 155-157, the claims further limit elements of alternative (i) of claim 116. Motz anticipates the embodiments of claims 155-157 in which the cell composition is administered.
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 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 Crompton (Cellular and Molecular Immunology. 2016. 13:502-513; published online on 4/27/2015; cited on the 2/1/2024 IDS).
Regarding claim 113, Xu teaches determining a phenotype property of a population of cells CD8+CD45RA+CCR7+ 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).
Regarding claim 114, Xu teaches comparing phenotypes and outcomes between different groups, with groups serving as references for one another.
Regarding claim 115, as noted above, Xu teaches the outcome is the persistence of the cells which is the basis for the durability of the response.
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).
Regarding claim 116, Xu teaches 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).
While Xu teaches the above methods, Xu does not teach determining an epigenetic property of the cells.
However, Crompton demonstrates that epigenetic properties of CD8+ T cells were known and could be used to distinguish different subtypes of CD8+ T cells.
It would have been prima facie obvious to the ordinary artisan to have modified the method of Xu by including an analysis of epigenetic properties of the CD8+CD45RA+CCR7+ T cells as compared to other CD8+ T cells as references in order to identify epigenetic properties that relate to the phenotype or functionality of CD8+CD45RA+CCR7+ T cells.
Claim 146 is/are rejected 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).
Claim 146 is/are rejected 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).
Regarding claim 146, Motz teaches determining an epigenetic property of genomic regions of a population of cells comprising a recombinant receptor by performing Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) to determine chromatin accessibility on enriched chimeric antigen receptor (CAR) positive CD8+ T cells (para. 1027).
Motz teaches Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) as noted above. An ATAC-seq process includes the steps of claim 145.
While Motz teaches the use of ATAC-seq, Motz does not teach determining fragments per kilobase per million mapped reads (FPKM).
However, Blatti teaches such a concept was known in the context of DNA accessibility and used in calculating chromatin accessibility scores (p. 4000). The value is used to quantify sequences.
It would have been prima facie obvious to have modified the method of Motz by incorporating the FPKM calculation of Blatti in order to calculate the number of times a region was found to be in an open state.
Claim 148 is/are rejected 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 Giresi (WO 2014/189957 A3)
Claim 148 is/are rejected 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 Giresi (WO 2014/189957 A3).
Regarding claim 148, Motz teaches determining an epigenetic property of genomic regions of a population of cells comprising a recombinant receptor by performing Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) to determine chromatin accessibility on enriched chimeric antigen receptor (CAR) positive CD8+ T cells (para. 1027).
While Motz teaches the use of ATAC-seq, Motz does not teach ChIP-seq.
However, Giresi teaches that ChIP-seq is used to confirm results from ATAC-seq (p. 6, 7, 8 and 9).
It would have been prima facie obvious to have substituted ATAC-seq of Motz for ChIP-seq based on Giresi demonstrating that the two assay are obvious variants of one another and can be used to confirm the results of each other.
Conclusion
No claims allowed.
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.
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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