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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05 August 2026 has been entered.
Status of the Claims
Applicant’s submission filed 05 August 2026 has been entered. Claims 1-8, 15-23, and 26-27 are pending. Claims 1, 4, 6-8, 22-23, and 26 have been amended. Therefore, prosecution on the merits continues for claims 1-8, 15-23, and 26-27. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
However, it is of note that the amendments to the claims filed on 05 August 2026 do not comply with the requirements of 37 CFR 1.121(c) because claims 1, 8, and 26 are listed as “Currently amended” without having any markings indicating the amendments that correct the claim objections of record in the Office action filed 08 April 2026, while claim 27 is listed at “Previously presented” despite having changes that were not properly marked. Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states (emphasis added):
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
(1) Claim listing. All of the claims presented in a claim listing shall be presented in ascending numerical order. Consecutive claims having the same status of “canceled” or “not entered” may be aggregated into one statement (e.g., Claims 1–5 (canceled)). The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment.
(2) When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. Only claims having the status of “currently amended,” or “withdrawn” if also being amended, shall include markings. If a withdrawn claim is currently amended, its status in the claim listing may be identified as “withdrawn—currently amended.”
(3) When claim text in clean version is required. The text of all pending claims not being currently amended shall be presented in the claim listing in clean version, i.e., without any markings in the presentation of text. The presentation of a clean version of any claim having the status of “original,” “withdrawn” or “previously presented” will constitute an assertion that it has not been changed relative to the immediate prior version, except to omit markings that may have been present in the immediate prior version of the claims of the status of “withdrawn” or “previously presented.” Any claim added by amendment must be indicated with the status of “new” and presented in clean version, i.e., without any underlining.
(4) When claim text shall not be presented; canceling a claim.
(i) No claim text shall be presented for any claim in the claim listing with the status of “canceled” or “not entered.”
(ii) Cancellation of a claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of a claim in the claim listing as “canceled” will constitute an instruction to cancel the claim.
(5) Reinstatement of previously canceled claim. A claim which was previously canceled may be reinstated only by adding the claim as a “new” claim with a new claim number.
As noted above, the amendment under consideration herein fails to comply with 37 CFR 1.121 because instant claims 1, 8, and 26-27 fail to correctly mark amendments and/or identify the status of the claims. Thus, the amendment could be considered non-responsive. However, in the interest of compact prosecution the amendment at issue will not be considered non-responsive. The Examiner notes that any future responses failing to comply with 37 CFR 1.121 will be held non-responsive, and will not be considered.
Status of Prior Rejections/Response to Arguments
RE: Objection to claims 1, 8, and 26-27
Applicant’s amendments to each of instant claims 1, 8, and 26-27 – though not properly marked – obviate the objections of record.
Therefore, the objections are withdrawn.
RE: Rejection of claims 1-7, 18-19, and 21 under 35 USC 102(a)(1) over Ma et al
Applicant’s amendments to independent claim 1 requiring the tissue-resident memory T cells to be cultured in the presence of IL-15, express CD103, CTLA-4, PD-1, have a reduced expression of Eomes, and demonstrate an enhanced persistence in tissue following adoptive transfer obviate the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 23 and 27 under 35 USC 102(a)(2) over Borrello et al
Applicant’s amendments to independent claim 23 requiring the tissue-resident memory T cells to be cultured in the presence of IL-15, express CD103, CTLA-4, PD-1, have a reduced expression of Eomes, and demonstrate an enhanced persistence in tissue following adoptive transfer obviate the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1-8, 18-21, and 26 under 35 USC 103 over Ma et al in view of Yee et al
Applicant’s amendments to independent claim 1 requiring the tissue-resident memory T cells to be cultured in the presence of IL-15, express CD103, CTLA-4, PD-1, have a reduced expression of Eomes, and have an enhanced persistence in tissue following adoptive transfer obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s remarks are addressed in so far as they are applicable to the claims as amended:
Applicant has traversed the rejection, asserting in Pages 8-9 of the Remarks filed 05 August 2026 that the combination of TGFβ, IL-7, and IL-15 enhances the migratory potential of the generated tissue-resident memory T cells, as evidenced by their CTLA-4 expression. Applicant points to Page 52 of the instant Specification to support this assertion. In response, the Examiner respectfully submits that the features upon which Applicant relies (i.e., enhanced migratory potential) are not recited in the rejected claims. Although the claims are interpreted in light of the Specification, limitations from the Specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In addition, the ordinary artisan would have reasonably expected the migratory potential to be enhanced within the tissue-resident memory T cells, as Milner et al (Curr Opin Immunol, 2019) teach that the tissue-resident memory T cells express CTLA-4. See 35 USC 103 rejection below.
RE: Rejection of claims 1-7, 15-16, 18-19, and 21-22 under 35 USC 103 over Ma et al in view of Xue et al
Applicant’s amendments to independent claim 1 requiring the tissue-resident memory T cells to be cultured in the presence of IL-15, express CD103, CTLA-4, PD-1, have a reduced expression of Eomes, and have an enhanced persistence in tissue following adoptive transfer obviate the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1-7, 17-19, and 21 under 35 USC 103 over Ma et al in view of Mansour et al
Applicant’s amendments to independent claim 1 requiring the tissue-resident memory T cells to be cultured in the presence of IL-15, express CD103, CTLA-4, PD-1, have a reduced expression of Eomes, and have an enhanced persistence in tissue following adoptive transfer obviate the rejection of record.
Therefore, the rejection is withdrawn.
New Grounds of Rejection
Claim Objections
Claims 6, 21, and 26 are objected to because of the following informalities:
Regarding claim 6: The instant claim is objected for reciting the “and/or” in between “cluster of differentiation 69 (CD69)” and “Hobit”, instead of in between “Hobit” and “aryl hydrocarbon receptor (AhR)”.
Appropriate correction is required.
Regarding claim 21: The instant claim is objected to for reciting “(TRM)” for the abbreviation of “tissue-resident memory T cells”, wherein the abbreviation of “(TRM)” is otherwise utilized throughout the claim language.
Appropriate correction is required.
Regarding claim 26: The instant claim is first objected to for reciting an inappropriate space between “(TGFβ)” and the following comma.
The instant claim is further objected to for a formatting issue, wherein part (v) of the claim is inappropriately spaced away from and not in line with parts (i)-(iv).
The instant claim is lastly objected to for reciting an extraneous period at the end of Line 11, which was not included in the amendment deleting the text preceding it. See MPEP § 608.01(m).
Appropriate correction is required.
Claim Interpretation
Under the broadest reasonable interpretation of each claim, the optional limitations in claims 5, 8, and 18 are not required.
Instant claims 23 and 27 are directed to a pharmaceutical composition comprising a therapeutically effective amount of an expanded population of tissue-resident memory T cells derived from a T lymphocyte cultured in the presence of transforming growth factor beta, IL-7, and IL-15, wherein the composition is a sterile solution or suspension suitable for intramuscular, intrathecal, epidural, intraperitoneal, intravenous and/or particularly subcutaneous injection administration, and exhibits the phenotypic and functional characteristics listed in (i)-(v). This is a product-by-process limitation. Product-by-process limitations are considered only in so far as the method of production affects the structure of the final product. In the instant case, there is no evidence that the culturing of the T lymphocyte in the presence of transforming growth factor beta, IL-7, and IL-15 imparts any particular structure or significance to the composition other than the cell being a tissue-resident memory T cell. Thus, the claims will be interpreted as if a sterile pharmaceutical composition comprising tissue-resident memory T cells derived from any source or production method fulfills the recited claim limitations, so long as the tissue-resident memory T cells exhibit the phenotypic profile of (i)-(iv) as listed in instant claim 23. It is of note that the functional characteristic of (v) in instant claim 23 does not impact the structure of the tissue-resident memory T cells. See MPEP § 2113.
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 19, 23, and 27 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 claim 19: The instant claim recites the limitation "the regulatory T cell" in Line 1. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of a regulatory T cell in the instant claim or parent claim 1. Therefore, the ordinary artisan cannot readily determine the metes and bounds of the claim, thus rendering the scope of the claim indefinite.
Appropriate correction is required.
For the sake of compact prosecution, the instant claim will be interpreted as if it is dependent upon instant claim 2.
Regarding claim 23: The instant claim recites the terms “particularly” in Line 12. In the instant case, the term “particularly” is being treated as exemplary language. Therefore, the exemplary term “particularly” renders the instant claim indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d). For the sake of compact prosecution, the instant claim is interpreted as if the “particularly” language is a regular alternative within the listed routes of administration.
Instant claim 27 is dependent upon parent claim 23 and thus incorporates the deficiencies of the parent claim, rendering the scope of the claim indefinite for the same reasons.
Appropriate correction is required.
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.
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 1-8, 18-21, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Milner et al (Curr Opin Immunol, 2019) in view of Yee et al (WO 2020/081987 A1, of record on IDS filed 17 November 2022).
Milner et al is considered prior art under 35 USC 102(a)(1). Yee et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2), with a publication date of 23 April 2020.
Regarding claims 1 and 3: Milner et al disclose transcriptional regulators or tissue-resident memory CD8+ T cells (Abstract).
As such, Milner et al disclose that CD8+ T cells are differentiated into tissue-resident memory T cells that express CD103, CTLA-4, PD-1, and have a reduced expression of Eomes (Pages 2, 4). Milner et al further disclose that the expression of CD103 in the tissue-resident memory T cells enables an enhanced retention and survival – or persistence – of the cells within tissue (Pages 3-4).
Milner et al further disclose that IL-15, IL-7, and TGFβ are required for the promotion and long-term maintenance of tissue-resident memory T cells (Pages 4-5).
Milner et al do not disclose culturing the CD8+ T cells in vitro with the IL-15, IL-7, and TGFβ to produce the tissue-resident memory T cells, as required in instant claim 1.
Yee et al, however, disclose the production of tissue-resident memory T cells in vitro via culturing naïve CD8+ T cells with TGF-β and IL-15 (Paragraphs [005], [007]-[008], [0010], [0036]-[0037], [0045], [0080], [00102], [00121]; Figures 1-2).
Yee et al further disclose that growth factors known to promote the growth and activation of tissue-resident memory T cells comprise IL-2, IL-7, IL-15, and IL-12, which include the combination of IL-2 and IL-7; IL-7 and IL-15; and IL-2, IL-7 and IL-15 (Paragraph [0080]).
Therefore, it would have been prima facie obvious to have modified the method of Milner et al such that the CD8+ T cells are cultured in vitro with IL-15, IL-7, and TGFβ to produce the tissue-resident memory T cells, as suggested in Yee et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to generate the tissue-resident memory T cells using in vitro culture methods, as it allows for the generation of the tissue-resident memory T cells outside of the body, and would have had a reasonable expectation of success given that the disclosure of Milner et al teaches that IL-15, IL-7, and TGFβ are required for the promotion and long-term maintenance of tissue-resident memory T cells, while the disclosure of Yee et al reasonably suggest in vitro culture methods using IL-15, IL-7, and TGFβ to produce tissue-resident memory T cells. See MPEP § 2143(I)(G).
Consequently, Milner et al as modified by Yee et al render obvious a method of producing tissue-resident memory T cells, wherein naïve CD8+ T cells (claim 3) are cultured in the presence of IL-15, IL-7, and TGFβ to produce the tissue-resident memory T cells, wherein the tissue-resident memory T cells express CD103, CTLA-4, PD-1, have a reduced expression of Eomes, and have an increased persistence in tissue. This therefore renders obvious the method of instant claim 1.
Regarding claims 2 and 19: Following the discussion of claim 1, the disclosures of Milner et al and Yee et al are each silent to the co-culture of the T cells with regulatory T cells (claim 2). As the regulatory T cells are absent, this therefore reads on the method of instant claim 19.
Regarding claim 4: Following the discussion of claim 1, Yee et al further disclose that TGFβ is present at a concentration of 0.1 to 5 ng/mL, while the concentration of IL-15 is 5-20 ng/mL (Paragraphs [0010]-[0011], [0097], [0102]). This therefore renders obvious the method of the instant claim for the same reasons as discussed in the rejection of instant claim 1. See MPEP § 2131.03.
Regarding claim 5: Following the discussion of claim 1, Yee et al further disclose that the naïve CD8+ T cells are human naïve CD8+ T cells (Paragraphs [0037]-[0038], [0046]-[0047], [0097]-[0101]). This therefore renders obvious the method of the instant claim for the same reasons as discussed in the rejection of instant claim 1.
Regarding claim 6: Following the discussion of claim 1, Milner et al further disclose that the tissue-resident memory T cells express CD69 (Pages 2, 4). This therefore reads on the method of the instant claim.
Regarding claim 7: Following the discussion of claim 1, Milner et al further disclose that the tissue-resident memory T cells are KLRG1lo (Pages 2-4). This therefore reads on the method of the instant claim.
Regarding claim 8: As aforementioned in the discussion of claim 1, Yee et al further disclose that growth factors known to promote the growth and activation of tissue-resident memory T cells comprise IL-2, IL-7, IL-15, and IL-12, which include the combination of IL-2, IL-7 and IL-15 (Paragraph [0080]). This therefore renders obvious the method of the instant claim for the same reasons as discussed in the rejection of instant claim 1.
Regarding claims 18 and 20: Following the discussion of claim 1, Yee et al further disclose the culturing of naïve CD8+ T cells in medium comprising mature dendritic cells (claim 20) presenting a viral antigen of interest (claim 18) (Paragraphs [008], [0010], [0024], [0026], [0033], [0045], [0048]). This therefore renders obvious the methods of the instant claims for the same reasons as discussed in the rejection of instant claim 1.
Regarding claim 21: Following the discussion of claim 1, Yee et al further disclose that the produced tissue-resident memory T cells are expanded (Paragraphs [0045], [00102], [00121]). This therefore renders obvious the method of the instant claim for the same reasons as discussed in the rejection of instant claim 1.
Regarding claim 26: As aforementioned in the discussion of claim 1, Milner et al as modified by Yee et al render obvious a method of producing tissue-resident memory T cells, wherein naïve CD8+ T cells are cultured in the presence of IL-15, IL-7, and TGFβ to produce the tissue-resident memory T cells, wherein the tissue-resident memory T cells express CD103, CTLA-4, PD-1, have a reduced expression of Eomes, and have an increased persistence in tissue.
With that, Milner et al further disclose that the presence of tissue-resident memory T cell gene expression is linked to a better prognoses in lung cancer patients (Page 6).
In addition, Yee et al further disclose that the produced tissue-resident memory T cells are administered to a subject suffering from lung cancer (Paragraphs [0008], [0025], [0029], [0056], [0066], [0072]-[0073]).
Therefore, it would have been prima facie obvious to have modified the method of Milner et al such that the produced tissue-resident memory T cells are administered to a subject suffering from cancer, as detailed in Yee et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to utilize the tissue-resident memory T cells as a cancer therapeutic, and would have had a reasonable expectation of success given that Milner et al teach that the presence of tissue-resident memory T cell gene expression is linked to positive clinical outcomes in subjects suffering from lung cancer. See MPEP § 2143(I)(G).
Consequently, Milner et al as modified by Yee et al render obvious a method of treating lung cancer within a subject, wherein tissue-resident memory T cells produced by culturing naïve CD8+ T cells in the presence of IL-15, IL-7, and TGFβ are administered to the subject, wherein the tissue-resident memory T cells express CD103, CTLA-4, PD-1, have a reduced expression of Eomes, and have an increased persistence in tissue. This therefore renders obvious the method of the instant claim.
Claims 1-8, 15-16, 18-22, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Milner et al (Curr Opin Immunol, 2019) in view of Yee et al (WO 2020/081987 A1, of record on IDS filed 17 November 2022), and further in view of Xue et al (J Nutr Biochem, 2007, of record).
The discussion of Milner et al as modified by Yee et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Milner et al as modified by Yee et al render obvious claims 1-8, 18-21, and 26. Xue et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 15-16 and 22: Following the discussion of claim 1 above, Milner et al further disclose that the CD8+ T cells may be splenic CD8+ T cells (Pages 2, 5).
The combination of Milner et al and Yee et al fail to teach the culturing of the CD8+ T cells in culture media comprising at least one aryl hydrocarbon receptor (AhR) ligand, as required by instant claim 15.
Xue et al, however, disclose the culture of splenocytes with 3,3’-Diindolylmethane (DIM) and IL-2, which enhanced the proliferation of the splenocytes compared to controls (Pages 337, 339-341; Figure 1). It is of note that the instant Specification lists diindolylmethane as a dietary derived aryl hydrocarbon. See Page 16 of the instant Specification.
Therefore, it would have been prima facie obvious to have modified the method of Milner et al in view of Yee et al such that the CD8+ T cells are cultured with DIM and IL-2, as detailed in Xue et al. One of ordinary skill before the effective filing date of the invention would have been motivated to culture the CD8+ T cells with compounds that enhance proliferation, and would have had a reasonable expectation of success given that the disclosures of Milner et al and Xue et al are concerned with the culture of splenic lymphocytes. See MPEP § 2143(I)(G).
Consequently, Milner et al as modified by Yee et al and Xue et al render obvious a method of forming tissue-resident memory T cells, wherein the CD8+ T cells are cultured in medium comprising DIM and IL-2 (claim 22). As DIM is inherently a dietary derived aryl hydrocarbon (claim 16), this therefore renders obvious the method of instant claim 15. See MPEP § 2112.
Claims 1-8, 17-21, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Milner et al (Curr Opin Immunol, 2019) in view of Yee et al (WO 2020/081987 A1, of record on IDS filed 17 November 2022), and further in view of Mansour et al (US 2021/0024882 A1, of record).
The discussion of Milner et al as modified by Yee et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Milner et al as modified by Yee et al render obvious claims 1-8, 18-21, and 26. Mansour et al is considered prior art under 35 USC 102(a)(2), with an effective filing date of 08 July 2019.
Regarding claim 17: Following the discussion of claim 1 above, Yee et al further disclose that the T cells are cultured within RPMI culture media (Paragraph [00102]).
The combination of Milner et al and Yee et al fail to teach that the culture media comprises at least one lipid, as required by instant claim 17.
Mansour et al, however, disclose improvements in cell culture methods (Abstract). As such, Mansour et al disclose the addition of lipids to basal culture medium to enhance the expansion of T cell subsets – including tissue resident memory T cells – wherein the basal culture medium is RPMI (Paragraphs [0052], [0060]-[0063], [0092], [0096], [0112], [0159]).
Therefore, it would have been prima facie obvious to have substituted the RPMI culture media of Yee et al with the RPMI culture medium comprising lipids of Mansour et al, as doing so would be a simple substitution of one known tissue-resident memory T cell culture medium for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two culture mediums are functionally comparable, as they both are comprised of RPMI basal medium and are utilized for the culture of tissue-resident memory T cells, and thereby would have been able to substitute the culture mediums with predictable results.
Consequently, Milner et al as modified by Yee et al and Mansour et al render obvious the culturing of the CD8+ T cells in culture medium comprising a lipid. This therefore renders obvious the method of the instant claim.
Claims 23 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Milner et al (Curr Opin Immunol, 2019) in view of Borrello et al (WO 2021/173948 A1, of record).
Milner et al is considered prior art under 35 USC 102(a)(1). Borello et al is considered prior art under 35 USC 102(a)(2), with an effective filing date of 28 February 2020.
Regarding claims 23 and 27: The instant claims comprise a product-by-process limitation that is interpreted as set forth above and incorporated herein.
Accordingly, Milner et al disclose transcriptional regulators or tissue-resident memory CD8+ T cells (Abstract).
As such, Milner et al disclose that CD8+ T cells are differentiated into tissue-resident memory T cells that express CD103, CTLA-4, PD-1, and have a reduced expression of Eomes (Pages 2, 4). Milner et al further disclose that the expression of CD103 in the tissue-resident memory T cells enables an enhanced retention and survival – or persistence – of the cells within tissue (Pages 3-4).
Milner et al further disclose that IL-15, IL-7, and TGFβ are required for the promotion and long-term maintenance of tissue-resident memory T cells (Pages 4-5).
Milner et al further disclose that developing approaches to induce tissue-resident memory CD8+ T cells is an attractive avenue for enhancing vaccine efficacy, and that the presence of tissue-resident memory CD8+ T cells is associated with an increased prognoses in lung cancer patients (Page 6).
Milner et al do not disclose a sterile pharmaceutical composition comprising a therapeutically effective amount of an expanded population of tissue-resident memory T cells suitable for intramuscular, intrathecal, epidural, intraperitoneal, intravenous and/or subcutaneous injection administration, as required by instant claim 23.
Borrello et al, however, disclose methods for enriching or isolating tumor specific marrow infiltrating lymphocytes (MILs), and compositions containing the MILs (Abstract).
As such, Borrello et al disclose that MILs comprise hypoxic-activated MILs, which include tissue-resident memory CD8+ T cells (Paragraphs [0004], [0037], [0042], [0068], [0070], [0110]; Example 1). Borrello et al further disclose sterile pharmaceutical compositions comprising a therapeutically effective amount of the hypoxic-activated MILs and a pharmaceutically acceptable excipient, wherein the sterile pharmaceutical composition is suitable for intramuscular, intravenous, or intraperitoneal administration (Paragraphs [0018], [0052], [0082], [0086]-[0087], [0089]).
Therefore, it would have been prima facie obvious to have modified the tissue-resident memory CD8+ T cells of Milner et al such that they are comprised within a sterile pharmaceutical composition with a pharmaceutically acceptable excipient, wherein the sterile pharmaceutical composition is suitable for intramuscular, intravenous, or intraperitoneal administration, as detailed in Borrello et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to produce a sterile pharmaceutical composition comprising the tissue-resident memory CD8+ T cells, as they can serve as a cancer therapeutic, and would have had a reasonable expectation of success given that the disclosure of Borrello et al teaches the formulation of a sterile pharmaceutical composition comprising tissue-resident memory CD8+ T cells. See MPEP § 2143(I)(G).
Consequently, Milner et al as modified by Borrello et al render obvious a sterile pharmaceutical composition comprising a therapeutically effective amount of CD103+CTLA-4+PD-1+Eomeslow/- tissue-resident memory CD8+ T cells and a pharmaceutically acceptable excipient (claim 27), wherein the sterile pharmaceutical composition is suitable for intramuscular, intravenous, or intraperitoneal administration. This therefore renders obvious the pharmaceutical composition of instant claim 23.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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/ALYSSA G WESTON/Examiner, Art Unit 1633
