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 .
Election/Restrictions
Claims 1-2, 4-5, 9, 12, 17, 31-32, 39, 41, 48, 50, 53-56, 66-69, and 72-75 are pending.
Applicant's election with traverse of Group I, corresponding to claims 1-2, 4-5, 9, 12, 17, 31-32, 39, 41, 48, 50, and 53-56, and species (a), the cytokines as in claims 4-5 in the reply on 12/12/2025 is acknowledged.
The traversal is on the grounds that, citing MPEP 803, there is no burden (Remarks, p2).
Applicant further argues that Groups I-IV have not been treated relative to making a showing of a lack of “unity of invention” as required by MPEP 1893.03(d) and 37 CFR 1.475 (Remarks, p2). In particular, Applicant argues that while lists different groups, it does not explain who each group lacks unity with each other group, specifically describing the unique special technical feature in each group (Remarks, p2-3). Continuing, Applicant argues that while the Examiner has made some general comments about the cited art, the Examiner has not by any reasonable measured established that what is asserted would have been obvious, thus permitting a conclusion of lack of unity with a reasonable expectation of success (Remarks, p2). Thus, Applicant concludes that the Examiner’s conclusory statements do not satisfy the burden of a prima facie assertion of obviousness under 35 USC 103 (Remarks, p3).
Applicant’s arguments, filed 12/12/2025 have been fully considered but are not found persuasive.
The establishment of “burden” is not required under 37 CFR 1.475(a) in a restriction requirement for a national stage application.
Furthermore, a demonstration of a prima facie case of obviousness is also not required not required under 37 CFR 1.475(a) in a restriction requirement for a national stage application.
Instead, as discussed in the Office Action, on 10/21/2025, as provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept ("requirement of unity of invention"). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression "special technical features" shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
As discussed in the Office Action on 10/21/2025, groups of inventions (Groups I-IV, see Office Action, p3) do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I-IV lack unity of invention because even though the inventions of these groups require the technical feature of a TIL culture medium comprising a cell culture ingredient, a cytokine, and an immune checkpoint antibody or an antigen-binding fragment thereof, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Fang (CN103374548, on IDS 11/28/2022) who teaches a serum free (a cell culture ingredient) TIL culture medium comprising IL-2 (a cytokine) and anti-CTLA-4 (a immune checkpoint antibody) (Abstract).
Thus, the requirement is still deemed proper and is therefore made FINAL.
Claims 9, 12, 17, 66-69, and 72-75 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/21/2025.
Claims 1-2, 4-5, 31-32, 39, 41, 48, 50, and 53-56 have been examined on their merits.
Claim Objections
Claim 41 is objected to for the following informalities: claim 41 ends with a redundant period. Appropriate correction is required.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 31 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 31 is the seed cell medium according to claim 1, wherein the immune checkpoint antibody or the antigen-binding fragment thereof is a PD-1 antibody or an antigen-binding fragment thereof, a LAG-3 antibody or an antigen-binding fragment thereof, a TIGIT antibody or an antigen-binding fragment thereof, or a CTLA-4 antibody or an antigen-binding fragment thereof. However, claim 1 already requires that the immune checkpoint antibody or the antigen-binding fragment thereof is a PD-1, LAG-3, TIGIT, or CTLA-4 antibody or antigen-binding fragment thereof. Therefore, claim 31 is not further limiting.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1-2, 4, 31-32, 39, and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fang et al. (CN103374548, 2013, on IDS 11/28/2022, previously cited).
In regards to claims 1 and 31, Fang discloses a serum free (a cell ingredient) TIL culture medium comprising IL-2 (a cytokine) and anti-CTLA-4 (an immune checkpoint antibody) (Abstract; claims 1 and 3).
In regards to claim 2, Fang discloses that the concentration if IL-2 is 1000U/ml (which is the same as 1000 IU/mL of IL2) (claim 2), which overlaps with the range of 3000 IU/mL or less.
In regards to claim 4, Fang discloses that composition may further comprise the cytokine IL-12 (claim 2).
In regards to claim 32, Fang discloses that the concentration of the CTLA-4 antibody is 3 µg/mL (claim 2), which overlaps with the claimed range of 1 µg/mL to 100 µg/mL.
In regards to claim 39, Fang discloses that the medium also comprises CD28 antibody (a costimulatory receptor antibody) (claim 1).
In regards to claim 41, Fang discloses that the concentration of anti-CD28 is 2 µg/mL (claim 2), which overlaps with the range of 3 µg/mL to 10 µg/mL as in claim 41.
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Fang et al. (CN103374548, 2013, on IDS 11/28/2022, previously cited) in view of Kim et al. (US20180228844A1, 2018).
Claims 1 and 4 are anticipated by Fang as discussed above.
In regards to claim 5, Fang teaches that the concentration of IL-12 is 7 pg/mL (claim 2). While it is unclear what this concentration is in U/mL, a person of ordinary skill in the art could have arrived at a concentration of 200 U/mL to 500 U/mL by routine optimization and the disclosure does not point to a criticality in this amount.
According to MPEP 2144.05(II)(A), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
In the instant case, because Kim teaches that T cells can be cultured in media comprising 150 IU/mL to 300 IU/mL IL-12 (paragraph [0092]), which overlaps with the range as in claim 5, a person of ordinary skill in the art could have arrived at a concentration of 200 IU/mL to 500 IU/mL by routine optimization with predictable results and a reasonable expectation of success.
Furthermore, it would have been predictably obvious to use a concentration of 150 IU/mL to 300 IU/mL IL-12, which lies within the claimed range because Fang teaches that this concentration can be added to T cell expansion media in order to promote development of T cell subsets (paragraph [0091]).
Therefore, the combined teachings of Fang and Kim renders the invention unpatentable as claimed.
Claims 48 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Fang et al. (CN103374548, 2013, on IDS 11/28/2022, previously cited) in view He et al. (Chinese Journal of Cancer, 2012).
Claim 1 is anticipated by Fang as discussed above.
In regards to claims 48 and 50, in regards to the limitation “The seed cell medium according to claim 1, wherein the serum-containing medium further comprises serum”, it is noted that claim 1 can be either a serum-containing medium or a serum-free medium. Therefore, claim 48 has been interpreted as requiring a serum-containing medium.
While, as discussed above, the medium as taught by Fang is serum-free, as taught by Fang, serum containing media is known in the art (p2 last paragraph to p3 top paragraph). A person of ordinary skill in the art would have been motived to use serum-containing conditions because serum contains growth factors and nutrients essential for cellular growth in vitro, and because He (cited by Fang at p2 last paragraph to p3 top paragraph) teaches that TILs can be effectively cultured in media comprising 5% serum (Generation of young TIL cultures, p288; a concentration of 5% serum lies within the concentration of 1% to 10%). Furthermore, because He teaches that TILs can be cultured in 5% serum, and because Fang cites He as teachings that it is known in the art that TILs can be cultured with serum, a person of ordinary skill in the art could have incorporated serum at a concentration between 1% and 10% into the composition of Fang, with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Fang and He renders the invention unpatentable as claimed.
Claims 53-55 are rejected under 35 U.S.C. 103 as being unpatentable over Fang et al. (CN103374548, 2013, on IDS 11/28/2022, previously cited) in view Thermo Fisher (Pen Strep, retrieved from Wayback Machine, 2017) and Hass et al. (Cancer Immunology Research, 2019).
Claim 1 is anticipated by Fang as discussed above.
In regards to claims 53-55, Fang does not explicitly teach that the medium comprises an antibiotic penicillin-streptomycin PS mixed solution. However, a person of ordinary skill in the art would have been motivated to use a penicillin-streptomycin PS mixed solution (Pen-Strep) in order to, as taught by Thermo Fisher prevent bacterial or fungal infections in culture (First page). A person of ordinary skill in the art would have been motivated to use a concentration that overlaps with the range of 1 U/mL to 200 U/mL because Haas teaches that T cells can be cultured in 1% (which is 100 U/mL) penicillin/streptomycin (Cell culture, pOF2) (see Thermo Fisher first page; stock Pen Strep has a concentration of 10,000 U/mL (first pag); 1% x 10,000 U/mL = 100 U/mL). Furthermore, because Pen Strep is a well-known antibiotic for cell culture, and because Hass specifically teaches that T cell can be cultured in pen strep, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Fang, Thermo Fisher, and Haas renders the invention unpatentable as claimed.
Claim 56 is rejected under 35 U.S.C. 103 as being unpatentable over Fang et al. (CN103374548, 2013, on IDS 11/28/2022, previously cited) in view Lynn et al. (US20200101108A1, 2020).
Claim 1 is anticipated by Fang as discussed above.
In regards to claim 56, Fang does not explicitly teach that the composition comprises a Treg inhibitor such as dasatinib. However, a person of ordinary skill in the art would have been motivated to include dasatinib because Lynn teaches that dasatinib prevents or reverses T cell exhaustion (paragraph [0013]. Furthermore, because Fang teaches that compositions for treating T cells can comprise dasatinib (claims 25 and 28), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Fang and Lynn renders the invention unpatentable as claimed.
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, 4-5, 31-32, 39, 41, 48, and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 13-16, 18 of copending Application No. 18/254,167 (reference application) in view He et al. (Chinese Journal of Cancer, 2012).
Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions are drawn to compositions for culturing TILs comprising at least IL-2 and a PD-1 antibody that are at least close to or could be optimized to the claimed concentration ranges.
While copending Application No. 18/254,167 does not specify whether conditions are serum-free or serum containing, a person of ordinary skill in the arts would have been motivated to use serum-containing conditions because serum contains growth factors and nutrients essential for cellular growth in vitro, and because He (cited by Fang at p2 last paragraph to p3 top paragraph) teaches that TILs can be effectively cultured in media comprising 5% serum (Generation of young TIL cultures, p288; a concentration of 5% serum lies within the concentration of 1% to 10%). Furthermore, because He teaches that TILs can be cultured in 5% serum, a person of ordinary skill in the art could have incorporated serum at a concentration between 1% and 10% into the composition with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 53-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 13-16, 18 of copending Application No. 18/254,167 (reference application) in view He et al. (Chinese Journal of Cancer, 2012) as applied to claim 1 above, and further in view of Thermo Fisher (Pen Strep, retrieved from Wayback Machine, 2017) and Hass et al. (Cancer Immunology Research, 2019).
In regards to claims 53-55, while copending Application No. 18/254,167 does not explicitly require the composition to comprise an antibiotic penicillin-streptomycin PS mixed solution. However, a person of ordinary skill in the art would have been motivated to use a penicillin-streptomycin PS mixed solution (Pen-Strep) in order to, as taught by Thermo Fisher prevent bacterial or fungal infections in culture (First page). A person of ordinary skill in the art would have been motivated to use a concentration that overlaps with the range of 1 U/mL to 200 U/mL because Haas teaches that T cells can be cultured in 1% (which is 100 U/mL) penicillin/streptomycin (Cell culture, pOF2) (see Thermo Fisher first page; stock Pen Strep has a concentration of 10,000 U/mL (first pag); 1% x 10,000 U/mL = 100 U/mL). Furthermore, because Pen Strep is a well-known antibiotic for cell culture, and because Hass specifically teaches that T cell can be cultured in pen strep, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 56 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 13-16, 18 of copending Application No. 18/254,167 (reference application) in view He et al. (Chinese Journal of Cancer, 2012) as applied to claim 1 above, and further in view of Lynn et al. (US20200101108A1, 2020).
In regards to claim 56, while copending Application No. 18/254,167 does not explicitly require the composition to comprise a Treg inhibitor such as dasatinib, a person of ordinary skill in the art would have been motivated to include dasatinib because Lynn teaches that dasatinib prevents or reverses T cell exhaustion (paragraph [0013]. Furthermore, because Fang teaches that compositions for treating T cells can comprise dasatinib (claims 25 and 28), it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 4-5, 31-32, 39, 41, 48, 50, and 53-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 21 of copending Application No. 18/254171.
Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions are drawn to compositions for culturing TILs comprising at least IL-2, PD-1 antibody, and serum that are at least close to or could be optimized to the claimed concentration ranges.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631