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 .
Priority
This application was filed 2nd of February 2024 and is a 371 application of PCT/CN2022/109577 filed on 2nd of August 2022, which claims foreign priority to PCT/CN2021110367 filed 3rd of August 2021.
Election/Restrictions
In the response filed on the 8th of July 2026, Applicant’s election without traverse of Group I, claims 1, 16, 18, 25, 28-29, 31, 34, 37-38, 40, 42-43, 49, 55, 70, and 151, drawn to a method of culturing tumor infiltrating lymphocytes (TILs) is acknowledged.
Claims 287, and 289-290 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8th of July 2026.
Claim Status
Claims 1, 16, 18, 25, 28-29, 31, 34, 37-38, 40, 42-43, 49, 55, 70, and 151 are under consideration in this office action.
Claim Objections
Claim 43 is objected to because of the following informalities: typo around the ratio where there is extra space placed after the semicolon. Appropriate correction is required.
Claim 70 is objected to because of the following informalities: typo or clarity. The claim 70 appears to repeat the phrase “the one or more T cell growth factors are one or more T cell growth factors,” therefore it is suggested to delete the second one or more T cell growth factors after the word “are”.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 15th of October 2024, and 8th of July 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Applicant is reminded of 37 CFR §1.56, which details Applicant's duty to disclose all information known to be material to patentability.
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement (see e.g. Cheng-Prusoff equation (Biochem. Pharmacol. (1973) 22:3099), page 40; and Brinkman et al, Nucl. Acids Res. (2014) page 142). 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Notably, the disclosure statements filed lists “International Searching Authority” reports (e.g. 10/15/2024). The list of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Specification
The use of the terms: Ficoll, e.g. page 124; “Stem Cell, Lonza, Thermo, Miltenyi etc.”, e.g. page 126, 134, and 160; Thermo Fisher, G-Rexl culture flasks, e.g. page 128; Lonza, e.g. page 128, 139; Miltenyi Biotech, Miltenyi, e.g. pages 139, 143, 146, 147, 160; Cure Genetics e.g. page 128; BD or Biolegend, e.g. page 130, 145, 146-147, 148, 156-157; Sigma, e.g. page 134 and 160; Beyotime, e.g. 135; eBioscience, e.g. page 139; Flowjo, e.g. page 140; Promega, e.g. 141, 143 CellTiter Glo, e.g. page 141; Lucigen, Sangon, Tiangen, e.g. page 141; Sartorius e.g. page 143; Corning, e.g. page 145; CellTiter-Glo Luminescent Cell Viability Assay, Promega) e.g. page 143; Beckman Coulter, e.g. page 148; and eBioscience, e.g. page 148), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
(Written Description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 70 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
Claim 70 recites “administering wherein the one or more T cell growth factors are one or more T cell growth factors selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ and the functionally active fragments thereof”(lines 1-3). However, the specification doesn't have adequate support in the disclosure for the generic T cell growth factors and their “functionally active fragments thereof” that characterizes any fragment thereof for T-cell growth factors for a method of culturing tumor infiltrating lymphocytes (TILs).
As written in the claim, the “functionally active fragments thereof” encompasses a broad genus of T-cell growth factors that includes various fragments from the one or more T cell growth factors selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ, and given its broadest reasonable interpretation in light of the specification corresponding to any T cell growth factors and their functionally active fragments thereof which encompasses functional and non-functional fragments thereof for the method of culturing tumor infiltrating lymphocytes (TILs).
Under the written description guidelines (see MPEP 2163), the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail so that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result, but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
In analyzing whether the written description requirement is met for a genus, “one or more T cell growth factors selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ and the functionally active fragments thereof”, the specification is first assessed to determine whether a representative number of species have been described by their complete structure of the genus.
As stated supra, claim 70 recites “administering wherein the one or more T cell growth factors are one or more T cell growth factors selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ and the functionally active fragments thereof”(lines 1-3). However, the specification doesn't have adequate support in the disclosure for the generic functionally active fragments thereof of the one or more T cell growth factors from the group consisting of IL-2, IL-7, IL-12, IL-15, IL-21, and interferon-γ.
The specification discloses that “In one embodiment, the T cell growth factors are one or more T cell growth factors selected from the group consisting of: IL-2 (the GeneID of the gene encoding it can be 3558), IL-4 (the GeneID of the gene encoding it can be 3565), IL-6 (the GeneID of the gene encoding it can be 3569), IL-7 (the GeneID of the gene encoding it can be 3574), IL-10 (the GeneID of the gene encoding it can be 3586), IL-12 (the GeneID of the gene encoding it can be 3592 or 3593), IL-15 (the GeneID of the gene encoding it can be 3600), IL-21 (the GeneID of the gene encoding it can be 59067), TNF-a (the GeneID of the gene encoding it can be 100137091), interferon y (the GeneID of the gene encoding it can be 3458), etc.”(see e.g. Spec. para. 224, 284, and page 57-58). Further, the specification discloses that the term "IL-2" or "IL2" generally refers to T cell growth factors known as interleukin 2 and comprises all forms of IL-2, which may comprise, in one embodiment, human and mammalian forms, conservative amino acid substitutions, glycoform modifications or variants, or active fragments thereof. The GeneID of the gene encoding IL-2 may be 3558” (see Spec. page 48).
However, the specification teaches “A complete culture medium was used, which may be optionally selected from X-vivo 15 culture medium or other commercially available T cell culture media, e.g. T cell culture media of Stem Cell, Lonza, Thermo, Miltenyi etc., and into which were added essential amino acids and antibiotics as well as IL-2 (SL Pharm) at an addition concentration of300 to 9000 IU/mL (e.g., the concentration may be 1000 to 9000 IU/mL, e.g., it may be 6000 IU/mL).”(Examples 1 on page 127 and Example 2 on page 129). Additionally, the specification discloses that “In the present application, the term "functionally active fragment" generally refers to a fragment having a partial region of a full-length protein or nucleic acid but maintaining or partially maintaining the biological activity or function of the full-length protein or nucleic acid. For example, a functionally active fragment may maintain or partially maintain the ability of the full-length protein to bind another molecule. For example, the functionally active fragment of the growth factor IL-2 may maintain or partially maintain the biologically active function of the full-length IL-2 to cause cell proliferation” (Specification, para. 428). Therefore, the specification fails to identify any functionally active fragments thereof of the one or more T cell growth factors from the group consisting of IL-2, IL-7, IL-12, IL-15, IL-21, and interferon-γ.
The method of making the claimed invention is not well established at the time of filling. However, one of ordinary skill in the art would neither expect nor predict the appropriate method of contacting the tumor infiltrating lymphocytes (TILs) with any functionally active fragment thereof from any of the T cell growth factor selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ as claimed using any functionally active fragment thereof.
The prior art of Tavera et al., (Journal of immunotherapy (Hagerstown, Md.: 1997) 41.9 (2018): 399.), discloses that it was well known in the prior art to the “first phase of expansion combined with an agonistic stimulation of CD137/4-1BB and IL-2 would favor preferential expansion of CD8+ TIL” (See e.g. abstract). Further, Tavera et al., discloses that addressing variability derived from culturing TIL with IL-2 alone by the combination of IL-2, agonistic CD137/4-1BB (Urelumab) and OKT3 antibodies (see e.g. discussions). Thus, Tavera et al., provides robust evidence that IL-2 was a known to be a predictable T-cell growth factor that would be cultured with TILs for a period of time. However, the post filing art of Burga et al., (Molecular Therapy 33.8 (2025): 3605-3623.) provides evidence that there are differences among the T-cell growth factors and fragments thereof. Burga et al., discloses that “Similar to IL-2, IL-15 can expand cytotoxic T cells and natural killer (NK) cells. Unlike IL-2, IL-15 does not expand regulatory T cells (Tregs), and that in contrast to IL-2, which can limit activated T-cell responses by promoting activation-induced cell death and terminal exhaustion, IL-15 promotes the survival and maintenance of memory CD8+ T cells, supporting a less-differentiated and more stem-like memory T-cell subset” (see e.g. page 3605-3607). Therefore, a person of ordinary skill in art would not be able to predict all of the functionally active fragment thereof of T-cell growth factors like IL-2 and IL-15, that would be suitable for culturing with TILs for a period of time. Thus, Burga et al., provides robust evidence that not all T-cell growth factors and their fragments thereof would be predictable or react similarly when culturing with TILs for a period of time. Further, the post filing art of Tovar Manzano et al., (Tumor-infiltrating lymphocyte expansion protocols for adoptive cell therapy in cancer. Cell Oncol (Dordr). 2025 Dec;48(6):1659-1675.) discloses that “in recent years, various modifications have been incorporated into the protocol with the aim of improving its efficiency, including the use of alternative combinations of cytokines such as IL-7, IL-15, and IL-21, as well as the replacement of irradiated feeder cells or anti-CD3 antibodies with other strategies” (see e.g. abstract). However, Manzano discloses that there are advantages and disadvantages of the interleukins IL-2, IL-7, IL-15, and IL-21 in the context of TILs therapy, and each interleukin plays a critical role in immune cell activation, proliferation, and differentiation, impacting the effectiveness of antitumor responses and understanding these factors is essential for optimizing TILs therapy and enhancing patient outcomes (see e.g. table 1, page 1663). Additionally, Manzano provides robust evidence that certain T-cell growth factors (i.e. interleukins) in the context of TILs are not predictable. Therefore, it would not have been predictable for a person of ordinary skill in art to be able to predict all of the functionally active fragment thereof that would be suitable for culturing with TILs for a period of time.
Therefore, with these additional evidence, the ordinary artisan cannot predictably identify any T-cell growth factor functionally active fragment thereof or what would be a non-functional fragment.
Furthermore, functionally defined genus claims can be inherently vulnerable for lack of adequate written description, especially in highly unpredictable technology fields, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
Given the breadth of any “functionally active fragment thereof,” that the claims embrace, a description of one species (i.e. IL-2), fails to provide a representative number of species that teaches the complete structure of the genus. Further the specification discloses “In one embodiment, the T cell growth factors are one or more T cell growth factors selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-y, and the functionally active fragments thereof”, and “in one embodiment, the T cell growth factors comprise IL-2 and/or a functionally active fragment thereof” (spec. para. 73-74). Therefore, an artisan of ordinary skill could not envision all the embodiments encompassed by the breadth of the claims. Consequently, any T-cell growth factor “functionally active fragment thereof” is not apparent to one of ordinary skill in the art from the description present in the specification. Therefore, an artisan of ordinary skill could not envision all the embodiments encompassed by the breadth of the claims.
Accordingly, the specification doesn't have adequate support in the disclosure for any functionally active fragment thereof from any of the T cell growth factor selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ as claimed using any functionally active fragment thereof. Similarly, the disclosure doesn't identify any functionally active fragment thereof from any of the T cell growth factor selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ as claimed using any functionally active fragment thereof. Therefore, the claimed recitation of any functionally active fragment thereof from any of the T cell growth factor selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ as claimed using any functionally active fragment thereof doesn't have an adequate written description. Furthermore, neither the specification nor the art indicates the predictability to identify any functionally active fragment thereof from any of the T cell growth factor selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ as claimed using any functionally active fragment thereof.
Therefore, it concludes that the claimed recitation of any functionally active fragment thereof from “any of the T cell growth factor selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ as claimed using any functionally active fragment thereof” doesn't have an adequate written description. Specifically, the specification does not identify the generic functionally active fragment thereof from any of the T cell growth factor selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-21, interferon-γ as claimed by using any functionally active fragment thereof. It concludes that a skilled artisan would find the specification inadequately described. Therefore, the Applicant did not sufficiently possess the broader invention as claimed.
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, 16, 18, 25, 28-29, 31, 34, 37-38, 40, 42-43, 49, 55, 70, and 151 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Benson et al., (WO2019/178420 A1, published Sept. 19, 2019, hereinafter as “Benson” cited IDS 10/15/2024).
Regarding claims 1, 49, 55, and 70, Benson discloses a method for culturing tumor infiltrating lymphocytes (TILs)(see e.g. Example 1), wherein the method comprises reducing the expression and/or decreasing the activity of at least one target gene of the TILs (see e.g. paras. 7, 137, 189, 229, 231, 296, Example 1 and 21-33), and co-culturing the TILs with feeder cells (see e.g. para. 390, 453, 507, 542 Examples 1, and 21-33), after contacting the TILs with one or more T cell activators (i.e. CD3(i.e. OKT3), CD28, HVEM, OX40L, OX40, and 4-1BB) and/or one or more T cell growth factors for a period of time (i.e. IL-2), corresponding to the claim limitations of one or more steps selected from the group consisting of: (1) adding the one or more T cell activators into the cell culture medium of the TILs; (2) adding engineered cells expressing the one or more T cell activators into the cell culture medium of the TILs (see e.g. para. 180-183, 386-387, 451-454, Examples 1 and 21-33).
Regarding claim 16, Benson discloses wherein the target gene comprises a gene encoding an NF-KB pathway inhibitory molecule (i.e. TRAF6)(see e.g. para. 9, 10, 17, 19, 163-167, 171, 250-252, 289; claims 1-8, 19, 34, 40, Tables 1-3, fig. 1, and Examples 1 and 21-33).
Regarding claim 18, Benson discloses wherein the NF-KB pathway inhibitory molecule comprises tumor necrosis factor-a-induced protein 3 (TNFAIP3)(see e.g. SEQ IDNO: 348-386; see e.g. paras. 9-10, claims 1-14, 19, 28, 33, Examples 1 and 21-33).
Regarding claim 25 and 28, Benson discloses wherein the method further comprises subjecting TILs derived from tumor tissues and not expanded in vitro to at a first and second state of in vitro expansion (e.g. introducing gene-regulating system or cryopreservation, see e.g. para. 104, 378, 296, 451-508, Example 32), and where the TILs are co-cultured with the feeder cells during a first and second round of in vitro expansion (see e.g. para. 185, claims 1-14, 19, 28, 33, 268, Examples 1 and 21-33).
Regarding claim 29 and 31, Benson discloses wherein the first stage and/or second stage of in vitro expansion is carried out for at least about 14 days (i.e. two weeks)(see e.g. para. 184-187 390-392, 453, and 508, and Examples 1 and 21-33).
Regarding claim 34, Benson discloses wherein the method comprises co-culturing the TILs with the feeder cells after contacting the TILs with the one or more T cell activators (e.g. CD3 (i.e. OKT3)) for (c) about 48 hours (see e.g. para. 545, page 191; Examples 1 and 21-33).
Regarding claim 37-38, Benson discloses wherein the feeder cells are antigen-presenting cells, such as peripheral mononuclear cells (PBMCs)(see e.g. para. 390 and 453, and Examples 1 and 21-33).
Regarding claim 40, Benson discloses wherein the feeder cells are irradiated feeder cells (see e.g. para. 390, 453, and 508, and Examples 1, 21, and 31-33).
Regarding claim 42, Benson discloses wherein the step of coculturing the TILs with the feeder cells comprises adding the feeder cells into the cell culture medium of the TILs (see e.g. para. 390, 453, and 508, Examples 1, 21, and 31-33).
Regarding claim 43, Benson discloses wherein the method comprises adding the feeder cells into the cell culture medium of the TILs at a ratio of the feeder cells to the TILs from about 40:1 to about 400:1 (i.e. 100:1) (see e.g. para. 390, 453, and 508, Examples 1, 21, and 31-33).
Regarding claim 151, as stated supra, Benson discloses a method for culturing tumor infiltrating lymphocytes (TILs)(see e.g. Example 1), wherein the method comprises: (1) reducing the expression and/or decreasing the activity of at least one target gene of the TILs and contacting the TILs with a CD28 agonist (e.g. anti-CD3/CD28/CD2 T-cell activator, and anti CD28 antibodies, Dynabeads™)(see e.g. paras. 444, 454, 605, Example 1 and 21-33).
Thus, Benson anticipates the instant claims.
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, 16, 18, 25, 28-29, 31, 34, 37-38, 40, 42-43, 49, 55, 70, and 151 are rejected on the ground of provisional nonstatutory double patenting as being unpatentable over claims 1, 3, 6, 8, 10, 13, 19, 20, 24, 26, 32, 38-39, 42-43, 46, 51, 100-102, and 104-106 of co-pending Application Number 18/269,407 (the ‘407 application).
Although the conflicting claims are not identical, they are not patentably distinct from each other because both claims sets are directed to a method for culturing tumor infiltrating lymphocytes (TILs), wherein the method comprises reducing the expression and/or decreasing the activity of at least one target gene of the TILs, and co-culturing the TILs with feeder cells after contacting the TILs with one or more T cell activators and/or one or more T cell growth factors for a period of time (see claim 1).
The co-pending ‘407 application’s claims are directed to a method for culturing tumor-infiltrating lymphocytes (TILs), comprising subjecting TILs derived from tumor tissues and not expanded in vitro to at least one stage of in-vitro expansion, and wherein the method comprises contacting the TILs with a CD28 agonist in at least one stage of the in vitro expansion (see claim 1).
Thus, the methods both use a method for culturing tumor-infiltrating lymphocytes (TILs), with a CD28 agonist, and the method of the ‘407 application would not be possible to use without the use of the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 16, 18, 25, 28-29, 31, 34, 37-38, 40, 42-43, 49, 55, 70, and 151 are rejected on the ground of provisional nonstatutory double patenting as being unpatentable over claims 1, 19-20, 38, 43, 46-47, 49, 51, 55, 56, 58, 60-61, 66, 69, 73, 88-89, 184, 351, 353, 355, and 357 of co-pending Application Number 18/556,511 (the ‘511 application).
Although the conflicting claims are not identical, they are not patentably distinct from each other because both claims sets are directed to a method for culturing tumor infiltrating lymphocytes (TILs), wherein the method comprises reducing the expression and/or decreasing the activity of at least one target gene of the TILs, and co-culturing the TILs with feeder cells after contacting the TILs with one or more T cell activators and/or one or more T cell growth factors for a period of time (see claim 1).
The co-pending ‘511 application’s claims are directed a method for culturing tumor-infiltrating lymphocytes (TILs), wherein the method comprising: improving the expression and/or enhancing the activity of at least one cytokine of the TILs, and co-culturing the TILs with feeder cells after contacting the TILs with T cell activators and/or T cell growth factors for a period of time (see e.g. claim 1).
Thus, the methods both use a method for culturing tumor-infiltrating lymphocytes (TILs), with a T cell activators and/or T cell growth factors for a period of time, and the method of the ‘511 application would not be possible to use without the use of the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 16, 18, 25, 28-29, 31, 34, 37-38, 40, 42-43, 49, 55, 70, and 151 are rejected on the ground of provisional nonstatutory double patenting as being unpatentable over claims 1, 3, 7, 9, 14-15, 17-18, 25, 27-28, 38, 40-41, 43-47 and 51of co-pending Application Number 18/827,527 (the ‘527 application).
Although the conflicting claims are not identical, they are not patentably distinct from each other because both claims sets are directed to a method for culturing tumor infiltrating lymphocytes (TILs), wherein the method comprises reducing the expression and/or decreasing the activity of at least one target gene of the TILs, and co-culturing the TILs with feeder cells after contacting the TILs with one or more T cell activators and/or one or more T cell growth factors for a period of time (see claim 1).
The co-pending ‘527 application’s claims are directed to a method for culturing tumor infiltrating lymphocytes (TILs), comprising co-culturing expanded TILs with feeder cells after contacting the expanded TILs with one or more T cell co-stimulatory molecule’s and/or one or more T cell growth factors for a period of time (see claim 1).
Thus, the methods both use a method for culturing tumor-infiltrating lymphocytes (TILs), with a one or more T cell co-stimulatory molecule’s and/or one or more T cell growth factors for a period of time, and the method of the ‘527 application would not be possible without the use of the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 16, 18, 25, 28-29, 31, 34, 37-38, 40, 42-43, 49, 55, 70, and 151 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-24 of the U.S. Patent No. US12110506 B2 (the ‘506 application) in view of Benson et al., (WO2019/178420 A1, published Sept. 19, 2019, hereinafter as “Benson” cited IDS 10/15/2024).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the competing claims are drawn to a disclosed species of the instant claims.
The instant claims are directed to a method for culturing tumor infiltrating lymphocytes (TILs), wherein the method comprises reducing the expression and/or decreasing the activity of at least one target gene of the TILs, and co-culturing the TILs with feeder cells after contacting the TILs with one or more T cell activators and/or one or more T cell growth factors for a period of time (see claim 1).
The patented claims are directed to a method for culturing tumor infiltrating lymphocytes (TILs), wherein the method comprises subjecting TILs that are derived from tumor tissues and not expanded in vitro to at least one stage of in vitro expansion, and wherein a single stage of the in vitro expansion comprises co-culturing non-in vitro-expanded or in vitro-expanded TILs with feeder cells after contacting the non-in vitro-expanded or in vitro-expanded TILs with one or more T cell co-stimulatory molecules and one or more T cell growth factors for a period of time, wherein the period of time is 12 hours or more (see claim 1). Further, the method according to claim 1, wherein the method comprises subjecting the TILs that are derived from the tumor tissues and not expanded in vitro to at least two stages of the in vitro expansion, and wherein the second stage of the in vitro expansion comprises co-culturing in vitro-expanded TILs with the feeder cells after contacting the in vitro-expanded TILs with the one or more T cell co-stimulatory molecules and the one or more T cell growth factors for the period of time (claim 2). Further, the method according to claim 1, wherein the one or more T cell co-stimulatory molecules are one or more of the molecules selected from the group consisting of: CD80, CD86, B7-H3, 4-1BBL, CD27, CD30, CD134, B7h, CD40, LIGHT, an antibody that specifically binds to CD3, an antibody that specifically binds to CD28, an antibody that specifically binds to HVEM, an antibody that specifically binds to CD40L, an antibody that specifically binds to OX40, and an antibody that specifically binds to 4-1BB (see claim 6).
Both claims are direct to a method for culturing tumor infiltrating lymphocytes (TILs), wherein the method comprises, and co-culturing the TILs with feeder cells after contacting the TILs with one or more T cell activators and/or one or more T cell growth factors for a period of time
The co-pending claims do not recite reducing the expression and/or decreasing the activity of at least one target gene of the TILs.
However, reducing the expression and/or decreasing the activity of at least one target gene of the TILs would have been obvious in view of the prior art in view of Benson.
Benson discloses a method for co-culturing the TILs with feeder cells (see e.g. para. 390, 453, 507, 542 Examples 1, and 21-33), after contacting the TILs with one or more T cell activators (i.e. CD3(i.e. OKT3), CD28, HVEM, OX40L, OX40, and 4-1BB) and/or one or more T cell growth factors for a period of time (i.e. IL-2), corresponding to the claim limitations of one or more steps selected from the group consisting of: (1) adding the one or more T cell activators into the cell culture medium of the TILs; (2) adding engineered cells expressing the one or more T cell activators into the cell culture medium of the TILs (see e.g. para. 180-183, 386-387, 451-454, Examples 1 and 21-33).
One would have used the co-pending methods in view of the teachings of the cited prior art for the benefits of modifying immune effector cells to increase therapeutic efficacy (see e.g. abstract), as taught in the prior art. One would have been motivated to do so with a reasonable expectation of success because the cited prior art teaches that culturing tumor infiltrating lymphocytes (TILs)(see e.g. Example 1), wherein the method comprises reducing the expression and/or decreasing the activity of at least one target gene of the TILs (see e.g. paras. 7, 137, 189, 229, 231, 296, Example 1 and 21-33), enhance effector functions of the immune cells. Therefore, the instant claims would have been obvious in view of the patented claims and the cited prior art. In addition, it would not be possible to use the instant claims without the method of the patented claims.
Therefore, all of the limitations of the instant claims would have been obvious in view of the patented claims and Benson.
Conclusion
No claim is allowed.
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Josephine Gonzales PhD
Examiner
Art Unit 1638
/JOSEPHINE GONZALES/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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