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 14,17-20,26,31,33-34 are under examination.
Election/Restrictions
Applicant's election with traverse of Group II (Claims 14,17-20,26,31,33, and 34) directed to a process of manufacturing a T-cell population comprising CD49f with enhanced immune properties in the reply filed on October 29, 2025 is acknowledged. The traversal is on the ground that “Yang (the prior art reference cited in the restriction) does not disclose any process for manufacturing T cell populations enriched with CD49f+ T cells or that CD49f+ T cell enrichment confers enhanced immune properties, such as increased proliferation potential, stem-like phenotype, or improved persistence in vitro.” Applicants’ argument is not found persuasive because the technical feature in common among all three groups is a CD49f+ T cell enriched population. That particular type of CD49f+ T cell also inherently has enhanced immune properties such as increased proliferation potential, stem-like phenotype, and improved persistence in vitro.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-6,10-11,69,71-72, and 76 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Groups I and III, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on October 29th, 2025.
Specification
The brief drawing description section in the specification fails to describe Figure 3D. This needs to be corrected.
Drawings
The drawings are objected to because Figure 3D is not described in the brief drawing description of the specification. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 34 is objected to because of the following informalities: “aignal” should be –signal--. Appropriate correction is required.
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 14,17-20,26,31,33-34 are 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 claims 14,17-20,31,34 the phrase “for example” [e.g.] renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 14 recites, “A process of manufacturing a T-cell population comprising T-cells with enhanced immune properties (e.g. selected from one or more of an early memory phenotype, a stem-like phenotype, increased proliferative potential, increased survival and increased persistence in vivo, decreased differentiation, increased immune effector function, decreased immune effector dysfunction and increased responsiveness in immunotherapy).” The claims recite “e.g.” which means for example. It is unclear if the limitations present in parentheses after e.g. are required or optional.
Similarly, claim 17 recites “wherein T-cell containing sample is enriched for T-cells of interest, for example CD8+T, CD4+T cells, naïve T-cells, memory T cells, previously activated T-cells and/or tumor infiltrating lymphocytes.” It is unclear if the cells recited after “for example” are required or optional.
Claim 18 recites examples of specific central memory T cells. The claim recites “wherein the CD49f+ T-cells include CD49f+ memory T cells including CD49f+ central memory T cells (e.g., CD49f+CD27+CD28+ memory T-cells, CD49f+CD27+CD28+CD45RA+ memory T cells, etc.).” It is unclear if the limitations present in parentheses after e.g. are required or optional.
Claim 19 recites, “wherein the CD49f+ T cells have an early memory phenotype and/or stem-like phenotype (e.g., CD49f+ T cells are positive for TCF-1 (e.g. TCF-1hi) and/or LEF-1 (e.g. LEF-1hi) and optionally positive for one or both of Oct4 and Sox2)”. It is not clear if the limitations after “e.g.” are required or only mere examples.
Claim 20 recites “(e.g., a T-cell population that is not enriched for CD49f+ T-cells as defined above and elsewhere herein, or an isolated CD49f+ T-cell enriched T cell population as defined above and elsewhere herein).” It is not clear if the limitations after “e.g.” are required or only mere examples. Furthermore, claim 20 states that the control can be “an isolated or CD49f+ T cell enriched T cell population as defined above and elsewhere herein.” This limitation is indefinite because it sounds like the enriched population of CD49+ T cells and not the control.
Claim 31 recites “(e.g. a vector such as a viral vector including a retroviral vector such as a lentiviral vector)” and “a cytokine (e.g., an immune-stimulatory cytokine).” It is not clear if the limitations after “e.g.” are required or not.
Claim 34 recites (e.g., scFv), (e.g., a hinge region of IgG1 or CD8α), and (e.g. an IgG1 heavy chain signal polypeptide or a CD8α aignal [signal] polypeptide). It is not clear if the limitations after “e.g.” are required or not.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP §2173.04c. In the present instance, claim 14 recites the broad recitation “at least 1% (including at least 2% to at least 99% and all integer therebetween).” The limitation in parentheses is a more narrow limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) required of the claim.
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 14,17-20,26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gattinoni et al. “A human memory T-cell subset with stem cell-like properties” Nat. Med: 17(10): 1290-1297”.
Gattinoni teaches enriching a sample containing stem memory T cells (TSCM) (Abstract, Pages 2-4 of Gattinoni), thereby manufacturing a T-cell population comprising T-cells with enhanced immune properties (Abstract and Pages 2-4 of Gattinoni). Gattinoni’s cells are enriched for the memory T phenotype (Pages 3-5 of Gattinoni)
The cells of Gattinoni are positive for BCL-2, LFA-1, CXCR3, CXCR4, CD38, CD31, CD45RA, CCR7, CD27,IL2Rα, IL2Rβ, IL7Rα,CD69,41BB, CCR5, CD28,CD57, and CD95 (Central memory cell markers) (Page 3 and Figure 1 of Gattinoni). The Gattinoni reference does not specify that the cells are also positive for CD49f+. However, Paragraph 8 of applicants specification states that such memory cells are also positive for CD49f+. Therefore, Gattinoni’s cells would inherently be positive for CDf49+. as in instant Claims14,17-18. Gattinoni discloses that the cells have a memory phenotype with a stem-like phenotype (Abstract of Gattinoni) as in instant Claim 19, Gattinoni teaches that its Tscm cell population has enhanced proliferative and survival capacities when compared to other types of T cells (Page 6, Increased Proliferative Capacity, Survival and Anti-Tumor Activity of TSCM cells) as in instant Claim 20. Gattinoni teaches exposing the TScm cells to stimulation/activation with a α-CD3,CD2,CD28 beads to produce antigen specific T cells (Page 3, TSCM possess attributes of convention memory section) as in instant Claim 26.
The reference anticipates the limitations in the claims.
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.
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 14,17-20,26,31,33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Gattinoni et al. “A human memory T-cell subset with stem cell-like properties” Nat. Med: 17(10): 1290-1297 in view of Dotti (US 20190048085) Modified Cells for Immunotherapy
Gattinoni applies as above to teach claims 14,17-20,26, Gattinoni states that its T cells can be combined with TCR (T-cell recptor) or CAR (chimeric antigen receptor) gene-engineering technology to treat and target cancer and infectious disease. Gattinoni does not teach more specific processes of developing CAR/TCR structures as claimed. Dotti teaches that a therapeutic strategy of engineering immune cells to express chimeric antigen receptors that are capable of targeting tumor cells involves developing a CAR T cell with an extracellular antigen recognition domain/ectodomain, a transmembrane domain, and an intracellular signaling domain (Paragraphs 4 and 54 of Dotti). The extracellular domain provides antigen recognition and is most commonly an antigen binding molecule (e.g. scFv) (Paragraph 54 of Dotti). In order to create such a CAR T-cell, a nucleic acid is delivered into the target T cell with an expression vector (a transduction process) (Paragraphs 173-175 of Dotti).
It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used the CAR construct method taught by Dotti to create the CAR T cell taught in Gattinoni. An artisan would have been motivated to have used Dotti’s CAR construct in order to effectively target cancer cells (Abstract of Dotti). There would have been a high expectation for success using the CAR structures taught in Dotti with the system taught in Gattinoni because the CAR structures taught in Dotti can effectively target cancer cells (Abstract of Dotti) as in instant Claims 14,31,33-34
Gattinoni teaches that its memory T cells can be combined with CAR gene engineering in order to produce a T cell that can successfully target cancers and/or infectious diseases. Gattinoni does not clearly describe a transduction process in which nucleic acid is successfully introduced into T cells to create a CAR T cell. However, an artisan would have been motivated to have used the transduction process taught by Dotti since uses a vector that is able to introduce nucleic acid into T cells to successfully form CAR T cells. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predicable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, cell culture, and immunotherapy. Therefore, the level of ordinary skill in this art is high.
Conclusion
All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638