Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 13, 2026 has been entered.
Applicant’s amendment filed on 17 February 2026 is acknowledged and entered.
Currently, claims 1, 3, 5, 7, 9, 12, 15, 21-23, 25-28, 30-32, 45, 47-49 are pending, and claims 7, 9, 12, 15, 21, 23, 25-28, 30, 45, 47 and 49 are under consideration. Claims 2, 4, 6, 8, 10-11, 13-14, 16-20, 22, 29, 33-44, 46 are canceled. Claims 1, 3, 5, 31, 32 and 48 remain withdrawn from further consideration as being drawn to a non-elected invention.
Rejections under 35 U.S.C. §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.
Claim 49 is 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 pre-AIA the applicant regards as the invention.
Claim 49 is indefinite for the recitation “(a) obtaining TILs from the mammalian subject” because it is unclear how TILs are obtained, or what the source of TILs is, if not from a body sample (as recited in claim 7), i.e., how it differs from claim 7? The obtaining TIL in claim 49 is generic to the subgeneric limitation of claim 7 of body sample. The metes and bounds of the claim, therefore, cannot be determined.
Applicants argue that page 23 of the specification disclose that TILs are a type of lymphocyte that is located in, on or around a tumor therefore TILs are also a type of “body sample” (i.e. lymphocyte). This is confusing because claim 49 limitation is generic to the subgeneric limitation of claim 7 of body sample. The specification page 23 obtaining of tumor is subgeneric to “body sample” thus is not clear how the tumor is a support for generic obtaining of TIL which would be generic to body sample.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Written Description/New Matter
Claims 7, 9, 12, 15, 21-23, 25-28, 30, 45 and 47 and 49 are 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 claim(s) 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 7 amendment is new matter because the specification pages 23, 26, and 30 do not provide support for the amendment. The previous claim 7 limitation was drawn to culture medium comprises the TAA, whereas the current amendment is not to add TAA to culture medium. Furthermore, page 23 paragraph is narrowly drawn TIL and its localization in the tumor and the method without expansion antigen generically whereas the claim 7 is not adding TAA in the generic culture medium. Page 26 of the specification paragraph is discussing the culture medium comprising at least one expansion antigen in addition to further defining the term and not discussion of not adding TAA as stated in claim 7. Page 30 of the specification uses the term “may” which applicants interpret as encompassing “not” adding TAA. However, the paragraph line in the specification states “may comprise least one expansion antigen” which is interpreted as adding the antigen.
Claims 7, 9, 12, 15, 21-23, 25-28, 30, 45 and 47 and 49 are 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 claim(s) 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The independent claims 7 and 49 recite “[A] method of selectively expanding a population of cells consisting of central memory CD45RA-CCR7+ T cells and peripheral memory CD45RA- CCR7- T cells from …”; however, applicant has not pointed out, nor can the Examiner locate, the basis in the specification for such a limitation. The specification teaches working examples of expanding T lymphocytes with the cytokine cocktail comprising 1000 U/ml IL-2, 10 ng/ml IL-15 and 10 ng/ml IL-21 (Example 1, for example), wherein body samples from cancer patients, such as blood and tumor tissues, are used as the original source of the T cells, and TILs were expanded from the tissue with the cytokine cocktail of IL-2, IL-15 and IL-21 (Examples 9-12, 27, 28, 31 and 32, for example). Analyses of the phenotype or differentiation of different T-cell subsets upon expansion were then carried out (Examples 11, 12, 31 and 32, for example), which shows that the expanded cells consisting of only central memory CD45RA-CCR7+ T cells and peripheral memory CD45RA- CCR7- T cells is not always the case. For example, Example 12 shows that CD45RA+ CCR7+ T cells and CD45RA+ CCR7- T cells can also be expanded under the same culture conditions (with different antigens); and that some antigens such as mesothelin particularly drive the expansion of precursor cells and defined by CD45RA+ CCR7+ and central memory cells defined by CD45RA− CCR7+ (page 50, Table 2, and last paragraph). Additionally, Example 16 shows an analysis of lymphocytes expanded from PBMCs of a patient with pancreatic cancer and from a patient with glioblastoma, wherein CD45RA- CCR7+ T cells (all subtypes tested) decreased significantly in the pancreatic cancer case, and CD45RA- CCR7- CD4 T cells decreased significantly in the glioblastoma case after the expansion (pages 55-56, Table 6). Further, Example 32 teaches that the results show in average a strong expansion of DN-T-Cells (data not shown), which subset is highly activated and bears affinity T-cell receptors; and also a strong expansion of CD45RA+CCR7+ precursor T-cell subsets is observed (page 70, lines 4-7). As such, the results of the claimed method are unpredictable, therefore, the specification does not provide adequate written description for the claimed method of selectively expanding a population of cells consisting of central memory CD45RA-CCR7+ T cells and peripheral memory CD45RA- CCR7- T cells from a body sample, which constitutes new matter.
Further, claim 49 recites “(a) obtaining TILs from the mammalian subject, (b) culturing the TILs in-vitro to expand …”; however, while applicant pointed out that the support for new claim 49 may be found on page 22, lines 15-24, of the specification, the examiner is not able to find the relevant disclosure in said location. Further, according to the specification, in order to obtain TILs, TILs were expanded first in vitro from tumor tissues (not the other way around, as claimed) with the cytokine cocktail of IL-2, IL-15 and IL-21 (see, for example, Examples 27, 28, 31 and 32). As such, the limitation is considered new matter.
Applicants argue that example 11 and 12 clearly shows expansion of T cells by the claimed methods does not occur in all types of T cells. However, the examples 11 and 12 does not support preamble limitations which are stated generically. The subgeneric term “selectively expanding a population of cells” is not supported. Specification has support for generic limitations and narrow species of example but not the subgeneric limitation of claim 7.
Prior Art Rejections
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 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.
Claim interpretation: as claim 49 is indefinite for the reasons above, and the examiner is not able to find the support for the limitation “(a) obtaining TILs from the mammalian subject”, this limitation is interpreted as being obtaining a body sample selected from peripheral blood and a tumor from the mammalian subject suffering from a tumor disease (like claim 7), since it is impossible not to obtain such a body sample first (which could comprise TILs).
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 of this title, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 7, 9, 12, 15, 21-23, 25-28, 30, 45, 47 and 49 remain rejected under 35 U.S.C. 103 as being unpatentable over Winqvist et al. (WO 2007/071390, 6/28/2007; provided by applicants), and further in view of Vella et al. (Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3810-5), and Zeng et al. (J Exp Med. 2005 Jan 3;201(1):139-48; provided by applicants), for the reasons of record set forth in the previous Office Actions mailed on 5/11/2023, 2/23/2024, 1/22/2025, 7/5/25.
Applicants argument filed on 17 February 2026 has been fully considered, but is not deemed persuasive for the reasons below.
Applicants argue that there is lack of motivation to add Il-15 and IL-21 to phase i) of Winqvist. Applicants argue that Winqvist teaches “gentle” expansion (“nursing phase”) and if IL-15 and Il-21 are added the result would be undesirable , non-specific expansion of clones that recognize irrelevant peptides. However, Winqvist state the “nursing phase” is where the tumour-reactive T-lymphocytes are brought to survive and divide. There is nothing in Winqvist to contradict such survival and division. Vella and Zeng provide the motivation to include the additional Il-15 and IL-21. The motivation does not have to be same as the applicant’s motivation.
Applicants argue that Winqvist also suggests the cells will not respond to IL-15 and IL-21 if these cytokines are added to the phase i) citing page 12. However, Winqvist does not discuss anything about IL-15 nor Il-21.
Applicants argue that Vella population of activated T cells are quite different from the T lymphocytes in the phase i) cultures of Winqvist. However, the teaching of IL-15 as important for survival is sufficient motivation.
Previous Arguments:
At pages 9-10 of the response, the applicant argues that claim 7 is amended to be directed to the selected expansion of only the two noted cells types from a body sample; and that none of the publications cited teach or suggest a method for the selective expansion of central memory CD45RA-CCR7+ T cells and peripheral memory CD45RA-CCR7- T cells, or even mentions these two cell types; therefore, the skilled artisan would not have looked to the cited art in an effort to expand these cells; and would not have been motivated to optimize the general parameters taught in the cited art, i.e. the specific parameters specified in step (c) of claim 7, to achieve the selective expansion of the two noted cell types.
This argument is not persuasive for the reasons of record and the following: first, the amended claim 7 and the new claim 49 recite “[A] method of selectively expanding a population of cells consisting of central memory CD45RA-CCR7+ T cells and peripheral memory CD45RA- CCR7- T cells from …” in the preamble, which represents the purpose of the claimed method, and can be resolved only on review of the entirety of the claim to gain an understanding of what being intended to encompass by the claim; and the amendment made no change in the actual method steps or active ingredients used, which are taught by the combined teachings of the prior art references for expanding tumor reactive T cells. While the prior art references do not mention or identify these cells by the marker as recited in the present claims, the method by the prior art is for the same purpose as that of the present invention, i.e., for expanding tumor reactive T cells, which cells various markers including but limited to CD45RA and CCR7, and can be identified by other molecules expressed. Naming or identifying same cells by different markers they express does not make these cells a different population. Given the fact that the prior art method of expansion uses the same starting material (a body sample from a cancer patient), and comprises the same or similar method steps and active ingredients, the resulted tumor reactive T cells from the expansion method of the prior art would inherently be CD45RA-CCR7+ and CD45RA- CCR7- T cells in the absence of any evidence to the contrary, as it is the method itself (the starting material, method steps and active ingredients), which determines its outcome, not an intended purpose. Thus, the burden is on applicant to provide evidence that the prior art method would not selectively expand CD45RA-CCR7+ and CD45RA- CCR7- T cells.
At pages 10-11 of the response, the applicant argues that even if the artisan had looked to the cited art, the artisan would not have had a reasonable expectation of success in selectively expanding just the two noted cells types from all of the other cell types that would be present in the body sample; would have reasonably expected that other cells in the body sample, such as other tumor-specific lymphocytes as suggested by the Examiner, would also be expanded; that given that the cited art fails to teach or even mention the two noted cell types, and the Examiner's suggestion that the cited art teaches a general expansion of tumor-specific lymphocytes, the cited art offers no degree of predictability whatsoever that the selective expansion of only two cell types would result from the combined teachings of the cited art.
This argument is not persuasive for the reasons of record and above. Once again, the amendment does not change the method itself, therefore, does not change the outcome of the method. Identifying the expanded T cells by the two phenotypes as recited, or lack thereof in the prior art references does not render the claimed method novel as discussed above, and the prior art references are not required to identify the same cells with the same markers.
Conclusion:
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL D PAK whose telephone number is (571)272-0879. The examiner can normally be reached on flexible time.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL D PAK/Primary Examiner, Art Unit 1674
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