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 .
Claim Status
Claims 1-20 are pending and under examination.
Claim Objections
Claims 5-7, 12-13, and 18-20 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claims 1, 8, 14, and 15 are objected to because of the following informalities: use of periods within the text of the claims to denote the steps “a.”, “b.”, “c.”, and “d.” Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-4 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.
Claim 1 recites the limitation "the tumor infiltrating lymphocytes" in line 4. There is insufficient antecedent basis for this limitation in the claim.
The claim refers to “the tumor infiltrating lymphocytes”, but the active method steps contain no earlier recitation or limitation providing a tumor infiltrating lymphocyte. Step 1a. is directed to administering an oncolytic virus into a tumor cell. Those skilled in the art could not reasonably ascertain the origin of the tumor infiltrating lymphocytes in the method as it does not state the method occurs in vivo, (i.e. intratumorally, systemically) or ex vivo in a culture that includes tumor infiltrating lymphocytes.
Dependent claims 2-4 are rejected for not providing limitations that overcome the 35 U.S.C. 112(b) rejection.
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.
(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.
Claims 1 and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Feist (Cancer Gene Ther 28, 98–111 (2021), cited in IDS 01/22/2024).
The disclosure of Feist is directed to investigating the effects of modified oncolytic viruses on the tumor microenvironment, teaching that local injection of an “IL-2 armed” oncolytic virus led to elicitation and accumulation of tumor-specific TILs in the tumor tissue (Abstract). Feist teaches that the TILs contained lower quantities of exhausted PD-1hi Tim-3+ CD8+ T cells and regulatory T cells. The isolated TILs from the oncolytic virus-treated tumor tissue retained high tumor specificity after expansion ex vivo (Abstract).
Regarding claim 1, pertaining to a method of generating tumor infiltrating lymphocytes comprising: (a) administering an oncolytic virus expressing one or more exogenous immunostimulatory molecules into a tumor cell; and (b) harvesting the tumor infiltrating lymphocytes, Feist teaches administration of an oncolytic viruses expressing different cytokines/chemokines and isolation of CD8+ TILs from the tumors (Pg. 101, Right column, Paragraph 2, Lines 1-12).
Regarding claim 14, pertaining to a method of treating a cancer in a subject comprising: (a) administering an oncolytic virus expressing one or more immunostimulatory molecule into a tumor cell; (b) harvesting the tumor infiltrating lymphocytes (TILs); (c) expanding the harvested TILs ex vivo; and (d) administering the expanded TILs to the subject, Feist discloses the following:
Administration of oncolytic viruses expressing different cytokines/chemokines and isolation of CD8+ TILs from the tumors (Pg. 101, Right column, Paragraph 2, Lines 1-12).
Culture of the harvested tumor infiltrating lymphocytes in the presence of IL-2 and IL-7, these expanded cells showing increased antigen-specificity and IFN-γ secretion compared to tumor infiltrating cells isolated from PBS-treated tumors (Pg. 104, Right column, “OV-induced TILs can be isolated from tumor tissues and expanded ex vivo” and Fig. 4a).
Adoptive transfer of oncolytic virus-induced TILs into a preclinical mouse model of colon cancer, demonstrating that TILs expanded with IL-2 armed oncolytic viruses showing a significantly increased survival rate compared to controls (Fig. 6C).
Claims 8, 11, and 15 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Veerapathran (US2018/0127715A1, published 05/10/2018, effectively filed 10/31/2016).
The disclosure of Veerapathran is directed to APCs transduced with viral vectors encoding immunostimulatory molecules, methods of expanding tumor infiltrating lymphocytes with the transduced APCs and subsequent cancer treatment using the expanded tumor infiltrating lymphocytes (Abstract).
Regarding claim 8 and 11, pertaining to a method of expanding a population of tumor infiltrating lymphocytes (TILs) comprising: (a) harvesting TILs from a subject with a cancer; (b) culturing the harvested TILs in the presence of antigen presenting cells infected with an oncolytic virus expressing one or more exogenous immunostimulatory molecules (claim 8), and wherein the one or more immunostimulatory molecules is selected from a list comprising CD86 (claim 11), Veerapathran discloses an antigen presenting cell transduced with one or more viral vectors comprising a nucleic acid encoding CD86 (Veerapathran claim 1) and a method of expanding a population of TILs comprising contacting the population of TILs with the APC population in cell culture (Veerapathran claim 17).
Regarding claim 15, pertaining to a method of treating a cancer in a subject comprising: (a) harvesting tumor infiltrating lymphocytes (TILs) from a subject with a cancer; (b) culturing the harvested TILs in the presence of antigen presenting cells infected with an oncolytic virus expressing one or more exogenous immunostimulatory molecules; and (c) administering the expanded TILs to the subject, Veerapathran further discloses a method of treating cancer with a population of TILs comprising the steps of: (a) obtaining a first population of TILs from a tumor resected from patient, (b) performing an initial expansion of the TILs, (c) performing a second expansion in the presence of the modified APCs, and (d) administering a therapeutically effective portion of the expanded TILs.
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.
Claims 1-4, 14, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Feist (Cancer Gene Ther 28, 98–111 (2021), cited in IDS 01/22/2024) as applied to claims 1 and 14 above and further in view of Beg (WO2019/246111A1, published 12/26/2019, effectively filed 06/19/2018, cited in IDS 01/22/2024).
The disclosure of Feist discloses the use of cytokine and chemokine-expressing oncolytic viruses in a method of expanding TILs and a method of treating cancer in a subject comprising administration of the expanded TILs.
The disclosure of Feist does not teach: that (1) the oncolytic virus expresses one or more type 1 interferons, (2) the one or more immunostimulatory molecules is selected from a list comprising CD40-L.
These deficiencies are taught by Beg.
The disclosure of Beg is directed to APCs comprising a combination of IFNβ and CD40-L, oncolytic viruses comprising a combination of IFNβ and CD40-L and methods for treating a malignancy by administering the oncolytic virus to a subject in need (Abstract). The oncolytic virus expressing the IFNβ and CD40-L demonstrated oncolytic effects on tumor cells lines in vitro.
Regarding claims 2-4 and 16-17, wherein the oncolytic virus further expresses one or more type I interferons (claims 2, 16), wherein the one or more type I interferon is selected from a list comprising IFN-β (claims 3, 17), and wherein the one or more immunostimulatory molecules is selected from a list comprising CD40-L (claim 4), Beg teaches an oncolytic adenovirus with dual expression cassettes encoding CD40-L and IFNβ (Fig. 2).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the methods of generating TILs and the method of treating cancer of Feist with the use of a modified oncolytic virus expressing IFNβ and CD40-L as taught by Berg. One would have been motivated to do so because Feist teaches the utility of cytokine-expressing oncolytic viruses for expanding tumor-specific tumor TILs for adoptive transfer and Berg teaches oncolytic viruses expressing IFNβ and CD40-L have antitumorigenic effects. There would be an expectation of success in combining the teachings of Feist and Berg because Feist shows evidence of the use of oncolytic viruses for expanding TILs and Berg teaches the generation of the IFNβ and CD40-L oncolytic virus constructs using methods widely used in the art at the time of filing.
Claims 8-11, and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Veerapathran (US2018/0127715A1, published 05/10/2018, effectively filed 10/31/2016) as applied to claims 8, 11, and 15 above, and further in view of Beg (WO2019/246111A1, published 12/26/2019, effectively filed 06/19/2018, cited in IDS 01/22/2024).
The disclosure of Veerapathran is directed to APCs transduced with viral vectors encoding immunostimulatory molecules, methods of expanding tumor infiltrating lymphocytes with the transduced APCs and subsequent cancer treatment using the expanded tumor infiltrating lymphocytes (Abstract).
The disclosure of Veerapathran does not teach: that (1) the oncolytic virus expresses one or more type 1 interferons, (2) the one or more immunostimulatory molecules is CD40-L.
These deficiencies are taught by Beg.
The disclosure of Beg is directed to APCs comprising a combination of IFNβ and CD40-L as well as oncolytic viruses comprising a combination of IFNβ and CD40-L and methods for treating a malignancy by administering the oncolytic virus to a subject in need (Abstract). The oncolytic virus expressing the IFNβ and CD40-L demonstrated oncolytic effects on tumor cells lines in vitro.
Regarding claims 9-11 and 16-17, wherein the oncolytic virus further expresses one or more type I interferons (claims 2, 16), wherein the one or more type I interferon is selected from a list comprising IFN-β (claims 3, 17), and wherein the one or more immunostimulatory molecules is selected from a list comprising CD40-L (claim 4), Beg teaches an oncolytic virus comprising an oncolytic adenovirus with dual expression cassettes encoding CD40-L and IFNβ (Fig. 2).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the methods of expanding TILs and the method of treating cancer of Veerapathran with the use of a modified oncolytic virus expressing IFNβ and CD40-L as taught by Berg. One would have been motivated to do so because Veerapathran teaches the utility of antigen presenting cells modified by oncolytic viruses for expanding tumor-specific TILs for adoptive transfer and Berg teaches oncolytic viruses expressing IFNβ and CD40-L have antitumorigenic effects. There would be an expectation of success in combining the teachings of Veerapathran and Berg because Veerapathran shows evidence of the use of oncolytic virus modified APCs for expanding tumor infiltrating lymphocytes and Berg teaches the generation of the IFNβ and CD40-L oncolytic virus construct using methods widely used in the art at the time of filing.
Conclusion
No claims are allowed.
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/CAROL ANN CHASE/Examiner, Art Unit 1646
/HONG SANG/Primary Examiner, Art Unit 1646
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