DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment, filed 06/05/2024, has been entered.
Claims 3-6, 9, 12-20, 23-28, 30-32, 35-36, 40, 42-96, 99-104, 107-109, 112-114, 118, 121-137, 139-147, 150-202 have been canceled.
Claims 1-2, 7-8, 10-11, 21-22, 29, 33-34, 37-39, 41, 97-98, 105-106, 110-111, 115-117, 119-120, 138, 148-149 are pending and currently under examination.
Independent Claims
1. (Original) A method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs, the method comprising:
(a) receiving a first population of TILs from at least a portion of a conditioned tumor resected from a subject by processing a tumor sample from the conditioned tumor into multiple tumor fragments, wherein a tumor in the subject is conditioned by administering an effective dose of an immunomodulatory molecule to the tumor and/or an effective dose of an oncolytic virus to the subject to produce the conditioned tumor prior to resection of the tumor sample from the conditioned tumor in the subject;
(b) expanding the first population of TILs into a therapeutic population of TILs by culturing the first population of TILs in a cell culture medium comprising IL-2; and
(c) harvesting the therapeutic population of TILs obtained from step (b).
33. (Original) A method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs, the method comprising:
(a) conditioning a tumor in a subject by administering an immunomodulatory molecule to the tumor and/or an oncolytic virus to the subject to obtain a conditioned tumor;
(b) obtaining a first population of TILs from at least a portion of the conditioned tumor by resecting the conditioned tumor from the subject and processing a sample obtained from the resection of the conditioned tumor into multiple tumor fragments;
(c) adding the tumor fragments into a closed system;
(d) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2, and optionally OKT-3, to produce a second population of TILs, wherein the first expansion is performed in a closed container providing a first gas-permeable surface area, wherein the first expansion is performed for about 3-14 days to obtain the second population of TILs, and wherein the transition from step (c) to step (d) occurs without opening the system;
(e) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, optionally OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed for about 7-14 days to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs, wherein the second expansion is performed in a closed container providing a second gas-permeable surface area, and wherein the transition from step (d) to step (e) occurs without opening the system;
(f) harvesting the therapeutic population of TILs obtained from step (e), wherein the transition from step (e) to step (f) occurs without opening the system; and
(g) transferring the harvested TIL population from step (f) to an Infusion bag, wherein the transfer from step (f) to (g) occurs without opening the system.
105. (Original) A method for treating a subject with cancer, the method comprising:
(a) obtaining a first population of tumor infiltrating lymphocytes (TILs) by processing a tumor sample obtained from resection of a tumor in the subject into multiple tumor fragments;
(b) expanding the first population of TILs into a therapeutic population of TILs;
(c) harvesting the therapeutic population of TILs obtained from step (b),
(d) administering a therapeutically effective dosage of the therapeutic population of TILs from step (c) to the subject; and
(e) administering an immunomodulatory molecule to the tumor and/or an oncolytic virus to the subject before, after, or before and after step (a).
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 1-2, 7-8, 10-11, 21-22, 29, 33-34, 37-39, 41, 97-98, 105-106, 110-111, 115-117, 119-120, 138, 148-149 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.
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 § 2173.05(c). In the present instance, claim 10, for example, recites the broad recitation “a cell culture medium comprising IL-2”, and the claim also recites “and optionally OKT-3” which is the narrower statement of the range/limitation. The “optionally” languages are also recited in claims 33, 34 and 105 with the similar issue as noted above. The claim(s) are 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) a required feature of the claims.
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 (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 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, 2, 7, 8, 105, 110, 111, 115 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Guo et al. (US 2020/0000862 A1).
Guo taught a method of expanding TILs comprising the steps of 1) conditioning the tumor by administering oncolytic virus encoding an immunomodulatory molecule to the subject or intratumorally; 2) receiving a first population of TILs from the tumor; 3) expanding the TILs into a therapeutic population of TIL by culturing in a medium with IL-2; and 4) harvesting the therapeutic population of TIL (see Summary of the Invention and paragraphs 0012-0017; 0019-0020, 0145, 0153, 0157). Guo further taught administering a checkpoint inhibitor (paragraph 0032). Moreover, Guo taught a method of treating a subject with cancer comprising administering a therapeutic population of TIL harvested from above expanding methods (paragraph 0162, 0165).
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 1-2, 7-8, 10-11, 21-22, 29, 33-34, 37-39, 41, 97-98, 105-106, 110-111, 115-117, 119-120, 138, 148-149 are rejected under 35 U.S.C. 103 as being obvious over Chartier-Courtaud et al. (WO 2019/210131 A1) in view of Guo et al. (US 2020/0000862 A1).
Chartier-Courtaud et al. taught a method of expanding TILs and producing therapeutic population comprising (a) obtaining a first population of TILs from a tumor resected from a patient by processing a tumor sample obtained from the patient into multiple tumor fragments; (b) adding the tumor fragments into a closed system; (c) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2, and optionally OKT-3, to produce a second population of TILs, wherein the first expansion is performed in a closed container providing a first gas-permeable surface area, wherein the first expansion is performed for about 3-14 days to obtain the second population of TILs, wherein the second population of TILs is at least 50-fold greater in number than the first population of TILs, and wherein the transition from step (b) to step (c) occurs without opening the system; (d) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, optionally OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed for about 7-14 days to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs, wherein the second expansion is performed in a closed container providing a second gas-permeable surface area, and wherein the transition from step (c) to step (d) occurs without opening the system; (e) harvesting the therapeutic population of TILs obtained from step (d), wherein the transition from step (d) to step (e) occurs without opening the system; (f) transferring the harvested TIL population from step (e) to an infusion bag, wherein the transfer from step (e) to (f) occurs without opening the system; and (g) at any time during the method, gene-editing at least a portion of the TILs, wherein said gene-editing cause silencing of an immune checkpoint gene (see, e.g., paragraphs 0005, 0055-0058). Furthermore, Chartier-Courtaud taught the step of cryopreserving the therapeutic population of TILs harvested using a 1:1 ratio of TIL population to cryopreservation media (paragraph 0006-0007). Moreover, Chartier-Courtaud taught a method of treating a subject with cancer comprising administering the therapeutic population of TILs harvested from the expansion steps mentioned above in combination with a checkpoint inhibitor such as pembrolizumab (paragraph 00574).
Chartier-Courtaud did not teach conditioning the tumor by administering an immunomodulatory molecule and/or an oncolytic virus to the subject as recited in the present claim (e.g., claim 1 step a). However, it would have been obvious to one of ordinary skill in the art to perform set conditioning step because it was well known in the art before the effective filing date of the claimed invention. For example, Guo et al. taught using an oncolytic virus to deliver immunomodulatory molecules intratumorally before collecting tumor samples for expansion of TILs (see above 102). Upon reading the teachings of Chartier-Courtaud and Guo, the ordinary artisan would have been motivated to condition the tumor by administering an oncolytic virus encoding an immunomodulatory cytokine which would be on a plasmid encoding the cytokine.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 7-8, 10-11, 21-22, 29, 33-34, 37-39, 41, 97-98, 105-106, 110-111, 115-117, 119-120, 138, 148-149 are rejected on the ground of nonstatutory double patenting as being unpatentable over the following claims of US Patents in view of Courtaud et al. (WO 2019/210131 A1) and of Guo et al. (US 2020/0000862 A1).
Patent
Claims
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The patent claims listed above disclosed a method of expanding TILs from a tumor into therapeutic population of TILs, method of treating cancer comprising administering the therapeutic population of TILs, and/or a composition comprising said therapeutic population of TILs. Therefore, it would have been obvious for one of ordinary skill in the art to arrive at the presently claimed methods in view of the teachings by Chartier-Courtaud and Guo as discussed above in 103. Therefore, the patent claims render obvious of the present claims in view of Chartier-Courtaud and Guo.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHARON X WEN whose telephone number is (571)270-3064. The examiner can normally be reached Mon-Fri 8-5.
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/SHARON X WEN/Primary Examiner, Art Unit 1641