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 .
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.
Election/Restrictions
Applicant’s election of Group I and the species FOXO1 in the reply filed on 7/7/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 28-29, 32-34, and 43-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/7/26.
Note that Applicant has declined to elect a species for the other required genera set forth in the Restriction requirement mailed 5/8/26. The Restriction Requirement did not indicate these elections were optional but rather that election is required even if traversing the requirement. This incomplete reply does not preclude examination currently and so an office action on the merits is provided. However, should these genera become necessary to examine (which may become the case as noted by Applicant in the 7/7/26 response), a notice of an incomplete reply will be sent if Applicant has not corrected this deficiency.
Claims 26-27, 30-31, and 35-42 are under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Notice
Applicant is advised that should claim 35 be found allowable, claim 38 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
In this case, the instant specification does not provide any special definition of a “kit” nor is there a standard definition in the art. The recitation “a kit” is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02. As such, claims 35 and 38 are duplicates.
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.
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.
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.
Claims 26-27, 30-31, 35, and 38-42 are rejected under 35 U.S.C. 103(a) as being unpatentable over Pule (WO 2016/193696; priority 5/31/2016; published 12/8/2016; IDS 1/12/24 FOR citation) in view of Gautam (WO 2017/035251; priority 8/24/2016; IDS 1/12/2024) and Stephan (US 2017/0296676; priority 4/14/2016; IDS 1/12/24 US citation).
Note that US 2019/0023761 (IDS 1/12/26 US citation) is being used as a corresponding document of WO2016/193696 and citations for Pule refer to the ‘761 document.
Note that US 2018/0258394 (form 892) is being used as a corresponding document of WO2017/035251 and citations for Gautam refer to the ‘394 document.
Regarding claim 1, Pule teaches a nucleic acid sequence encoding a chimeric antigen receptor (CAR) (claim 39). Pule teaches transduction of this nucleic acid into a cell including with the nucleic acid in a vector (paragraph 58). Pule also teaches including a second nucleic acid encoding a transcription factor (paragraphs 39, 49). See also paragraphs 161-175 for descriptions of cells comprising both nucleic acids.
Likewise, Gautam discloses T cell (a cell) for adoptive cell therapy comprising a nucleic acid encoding a chimeric antigen receptor (a first nucleic acid) and a nucleic acid sequence able to express a transcription factor at a level that is higher than the level of the transcription factor expressed by a T cell that has not been modified to express the transcription factor (a second nucleic acid) (claims 1, 2; paragraph 45).
One of ordinary skill in the art would have found it obvious at the time of filing to have a cell comprising a first nucleic acid encoding a CAR because both Pule and Gautam teach such cells. The person would have further found it obvious to include a second nucleic acid encoding a transcription factor because both Pule and Gautam teach such cells. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP § 2144.06(I). Additionally, Gautam teaches the actual combination of the CAR and transcription factor in the same cell (e.g., claim 1) making it obvious to put the nucleic acids for both in the same cell.
With respect to “exogenous”, the instant specification defines “exogenous” as “the nucleic acid molecule is made by recombinant means and is introduced into the cell by way of a vector” (specification p.19 C10-11). The phrase “made by” and “is introduced” are not describing properties of the composition itself but rather are product-by-process limitations, e.g., how the nucleic acid was made and how the nucleic acid arrived in the cell. For the instant composition of matter claims, any nucleic acid will meet the limitations of “made by recombinant means” as there does not appear to be any structural requirement for the recombinant nucleic acid to differentiate from nucleic acids made by other means. For the instant composition of matter claims, if the nucleic acid is in the cells as claimed, then the limitation of “is introduced by way of a vector” will be considered met as there does not appear to be a structural difference between the nucleic acid introduced by other means nor is the vector required to remain present in, e.g., claim 26. Burden is properly shifted to Applicant to demonstrate a non-obvious difference (MPEP §2113 (I-II)). Further, Gautam teaches recombinant and exogenous CARs (paragraph 43) and recombinant nucleic acids (paragraph 55) as well as including nucleic acids in vectors (paragraph 63-64). Pule teaches introducing the nucleic acids into the cell via vectors (paragraph 401). Thus, even in the case where “made by recombinant means” and “introduced by into the cell by way of a vector” are given patentable distinction, both of these limitations are taught by the prior art as a known means of making and introducing the nucleic acid making such steps obvious.
While both Pule and Gautam teach including transcription factors, neither teaches this transcription factor is FOXO1.
Stephan teaches FOXO1 is a transcription factor that regulates memory CD8+ T cells (paragraph 113). Memory precursor T-cells express higher amounts of FOXO1 which promotes the generation and maintenance of memory-precursor cells (paragraph 113). FOXO1 also facilitates effector-to-memory transition and functional maturation of CD4 and CD8 T-cells (paragraph 114).
It would have been obvious to one of ordinary skill in the art at the time of filing to include a nucleic acid encoding FOXO1 with a nucleic acid encoding a CAR arriving at the instant claim. Including the CAR and a transcription factor is discussed above. Pule teaches the cells discussed above are T-cells expressing CD8 (paragraph 435) and are memory T cells (paragraph 436). Gautam also teaches the cells are memory T cells (paragraph 35, 80) and express CD8 (claim 11; paragraph 8, 35, 103). It would have been obvious to include a nucleic acid encoding FOXO1 transcription factor to gain the same benefits for these T-cells as described by Stephan. This includes the direct teaching by Pule that “upon activation the T-cell may be programmed to express transcription factors which act to prevent the T-cell from differentiating” (paragraph 325), which is a result of expressing FOXO1 as taught by Stephan. An artisan would have had a reasonable expectation of success as expression of FOXO1 in T cells to induce surface markers such as CD62L and transcriptional patterns characteristic of CD8+ central memory T cells was known in the art before the effective filing date of the invention.
Regarding claim 27, this claim is directed solely to a property of the transcription factor. As the transcription factor is the same (FOXO1), the property must also be present. Chemical compounds and their properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966)). Further, the reduction of differentiation is taught as above.
Regarding claims 30-31, the transcription factor is FOXO1 as above and so is necessarily also a central memory repressor.
Regarding claim 35, this claim is broader than claim 26 since it does not require the nucleic acids are exogenous or in a cell. This claim would have been obvious for the reasons above.
Regarding claim 38, this claim is a duplicate of claim 35 because the preamble “a kit” is of no significance to the claim construction. A “kit” does not provide any structural limitations and the body of the claim is complete in itself.
Regarding claim 39, including the nucleic acids in a vector would have been obvious as above.
Regarding claim 40, including the nucleic acids in a vector would have been obvious as above. While the discussion of claim 26 presents reasoning that combining the separate nucleic acids into a single “construct” would have been obvious, it would similarly have been obvious to include individual vectors in the same cell as this is taught by the art as described above and the person of ordinary skill would have recognized that this achieves the same result.
Regarding claim 42, Pule teaches a plurality of cells of the invention as a pharmaceutical composition (paragraph 463), as does Gautam (claim 16), and Stephan (paragraph 176). It would have been obvious to prepare a population of cells as a pharmaceutical composition because the art teaches this is a known and appropriate formulation for the purposes described.
Regarding claim 41, the nucleic acids and vectors encoding the CAR and FOXO1 would have been obvious as above. The art also teaches introducing these nucleic acids/vectors into a cell as described above. This arrives at the instantly claimed method.
Therefore, claims 26-27, 30-31, 35, and 38-42 would have been obvious.
Claim(s) 36-37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pule (WO 2016/193696; priority 5/31/2016; published 12/8/2016; IDS 1/12/24 FOR citation) in view of Gautam (WO 2017/035251; priority 8/24/2016; IDS 1/12/2024) and Stephan (US 2017/0296676; priority 4/14/2016; IDS 1/12/24 US citation) as applied to claims 26-27, 30-31, 35, and 38-42 above, and further in view of Richmond (US20090222936; form 892).
The discussion of claims 26-27, 30-31, 35, and 38-42 are above and incorporated herein. While it would have been obvious to create a single construct with both the CAR and transcription factor genes as discussed above, the cited art does not teach a self-cleaving peptide separating the two.
Nevertheless, it would have been obvious, in the construct comprising the CAR gene and TF gene, to separate these two genes by a nucleic acid sequence that encodes a self-cleaving peptide. When set to create such a construct, one of ordinary skill in the art would have looked to known methods of co-expressing multiple genes from a single construct. Richmond is concerned with this same problem. Richmond teaches several co-expression systems have been developed for eukaryotic cells (which includes T-cells) and is successfully employed when using a single virus (paragraph 5). Richmond teaches a major improvement is in multigene cassettes (paragraph 6) where multiple vector subunits encoding different proteins were connected into a single vector, separating each gene by a self-cleaving peptide (paragraph 9). This arrangement is described throughout, including paragraph 13 and claim 1.
It would have been obvious to use the known arrangement of separating different genes encoding proteins by a nucleic acid encoding a self-cleaving peptide because the art teaches that a single nucleic acid construct expressing multiple proteins is a known technique for expressing these proteins and that separating them with a self-cleaving peptide leads to the expected expression and function of these proteins.
Therefore, claims 26-27, 30-31, and 35-42 would have been obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Adam Weidner/Primary Examiner, Art Unit 1675
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