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 .
Applicant’s response filed 6/8/2026 has been received and entered.
Claims 1-14, 17, 19, 20 are pending. Claims 1-11 are withdrawn. Claims 12-14, 17, 19, 20 have been considered on the merits. All arguments and amendments have been considered.
The following rejection is withdrawn in light of applicants amendments; Claim(s) 12,14, 17-20 rejected under 35 U.S.C. 103 as being unpatentable over Crespo et al. WO97/33975 (see translated document) in view of WO2019238143 (IDS), Yarmush et al., (US20140030231 A1) in further view of Baldan et al. (Br. J. of Cancer, 2015, vol. 112, p. 1510-1518) and Grange et al. (J. Immun. Methods, 2011, vol. 372, p. 119-126).
Maintained rejections
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.
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(s) 12-14, 17, 19, 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over JP2012116823 (IDS) in view of Crespo et al. WO97/33975 (see translated document) in further view of WO2019238143 (IDS), Yarmush et al., (US20140030231 A1), Baldan et al. (Br. J. of Cancer, 2015, vol. 112, p. 1510-1518) and Grange et al. (J. Immun. Methods, 2011, vol. 372, p. 119-126).
JP823 teaches a preservation solution and method comprising a solution for preserving biological tissue in a non-frozen state comprising albumin at a concentration of 0.1 to 5% (abstract), thus falling within applicants claimed concentration of 0.01-2%, lactic acid present in an amount between 15 to 150 mmol/L, thus falling within applicants claimed 0.1-100 mmol/L (p. 9, 2nd full parag.), sodium in amounts of 10-140 mmol/L, preferably 80-120 mmol/L (p. 5, 2nd and 3rd full parag., p. 6, 1st and 3rd full parag., p. 9, 1st and 2nd full parag.), thus falling within applicants claimed 50-300 mmol/L. The method comprises storing the tissue and cells in the preservation solution (p. 5, whole page, p. 22, 3rd parag., see entire document). The method and solution allow for extended preservation periods without deteriorating the function of the biological tissue and preserves the tissue immediately after extraction from a living body in a non-frozen state (p. 6, 2nd to last parag., p. 8, 2nd full parag.). Regarding claim 13, the composition is in a non-frozen state (p. 5, last parag.) and maintained between 2-15°C and close to 4°C (p. 6, 2nd full parag., p. 13, 1st parag., p. 22, 3rd parag.), thus falling within applicants claimed 0-4°C. JP823 teaches that the solution can be used to preserve any tissue extracted from the living body (p. 5, 1st full parag., p. 12, 1st parag.).
JP’823 does not teach the sample to comprise tumor cells or tissues.
WO97/33975 teaches a sample preservation method comprising placing a sample in a composition comprising albumin (HSA or BSA) (p. 3, 4th parag., p. 4, last parag.- p.5, whole page), sodium lactate present in an amount ranging from 0.5 to 4 g/L (p. 1, line 6) which equals a lactic acid ion concentration ranging from 4.46 to 35.7 mmol/L, thus falling within applicants claimed 0.1-100 mmol/L, and sodium, wherein the sodium ion (NaCl, for example) is present in an amount of 5.7 g/l which equals 97.5 mmol/L (p. 3, 6th-8th parag. Table 1, claims 1-6), thus falling within applicants claimed 50-300 mmol/L. The sample is disclosed to include B and T lymphocytes (CD4 and CD8 cytotoxic lymphocytes, tumor infiltrating lymphocytes, tumor cells and tumor biopsies (p. 7, 3rd parag., p. 92nd and 3rd parag.).
The above references do not teach treating the sample with an enzyme to obtain a target substance particularly tumor cells or tissue or mixtures thereof from a sample according to claims 14, 17, 19, 20.
However, enzymatic dissociation of tissue samples to obtain target cells is well-known in the art as taught by each of WO’143, Yarmush (US20140030231 A1), Baldan, and Grange.
WO2019238143 teaches obtaining a tumor tissue, storing the freshly excised tumor tissue in a sample preservation solution comprising Fetal Bovine serum which contains albumin (Table 1, preserv. Solution Gibco#16000-044 present in 2% is FBS, p. 13, (E1, E2), p. 33, Ex. 1 p. 14-16) and further treating tumor tissue with an enzyme to obtain tumor cells. The tissues are treated with a dissociation reagent comprising collagenase (p. 6, 12th parag., p. 9, 6th parag., p. 10, 4th parag. Method A step (a1)) and DNAse (p. 33-35, Ex. 14, Table 29).
Yarmush (US’231) teaches a method of sample preservation (0022- 0024) comprising preserving a sample (tissue) in a preservation solution comprising albumin, lactate and sodium (0256). The method further comprises isolating cells from the preserved sample by treating with an enzyme selected from collagenase, trypsin or hyaluronidase to obtain target cells (0270).
The above references do not teach the tumor cells to be tumor-infiltrating lymphocytes according to claim 14, 19 and analyzing the target cells using methods of claim 20.
Baldan teaches isolating tumor-infiltrating lymphocytes (TIL’s) from tumor biopsies using enzymatic disaggregation with DNAse, collagenase and hyaluronidase (p. 1511, Isolation and expansion of RCC TIL’s section). The TIL’s are analyzed using flow cytometry (p. 1511, Flow cytometry section).
Grange teaches the isolation and analysis of tumor infiltrating immune cells (TIIC) comprising treating tumor samples in a storage medium with collagenase or collagenase and DNase to obtain tumor infiltrating immune cells from the tumor samples (p. 120, 1st col., 1st full parag., section 2.1). The TIIC were analyzed by flow cytometry analysis (section 2.4, p. 122, Discussion section).
Thus, before the effective filing date of the claimed invention, the art teaches sample preservation solutions comprising albumin, lactate and sodium ions within the claimed concentration, for use in methods allowing for extended preservation periods without deteriorating the function of the biological tissue including tumor biopsies, and well-known methods for isolating target cells including tumor cells from tissue using enzymes. It would have been obvious to one of ordinary skill in the art to have used the tissue/cell preservation solution of the art which allows for extended preservation periods without deteriorating the function of the biological tissue and preserves the tissue immediately after extraction from a living body in a non-frozen state in methods of preparing a sample to obtain a target cell population because a person of ordinary skill in the art would have had good reason to preserve tissue samples which are to be used for further processing, i.e. to isolate a desired cell population. It would be well within the purview of the skilled artisan to pursue known options within his or her technical grasp to preserve tissue separated from the body, which decrease in physiological activity after separation and during storage, when using the tissue for further processing. Therefore, a posita would have had a reasonable expectation of successfully isolating a target cell population by enzyme treatment in tissues which have successfully been preserved in the solution as claimed.
Further enzymatic dissociation/disaggregation is well-known in the art and used for isolating desired cell types from tissue, including tumor cells (TIL’s) from tumor tissue/biopsies. Thus, a posita would have had a reasonable expectation of successfully preparing a tumor sample and obtaining a targeted cell type from tissue when practicing enzymatic dissociation/disaggregation disclosed by the art references of record.
Response to Arguments
Applicants’ arguments filed 6/8/2026 have been fully considered but they are not persuasive.
Applicant argues there is no motivation to combine the references as Crespo, Yarmush and WO’143 are silent regarding tumor infiltrating cells and thus the preservation of their state in a sample.
Crespo teaches a sample preservation method comprising placing a sample in a composition comprising albumin (HSA or BSA), sodium lactate, and sodium and the sample is disclosed to include B and T lymphocytes (CD4 and CD8 cytotoxic lymphocytes, tumor infiltrating lymphocytes, tumor cells and tumor biopsies, thus providing a composition and immersing the sample in said composition. Secondary references Baldan and Grange were relied upon for the teachings of the preparing a sample by treating with an enzyme to obtain a target cell, specifically TIL’s. Thus, enzymatic dissociation/disaggregation is well-known in the art and used for isolating desired cell types from tissue, including tumor cells (TIL’s) from tumor tissue/biopsies. Therefore, a posita would have had a reasonable expectation of successfully preparing a tumor sample and obtaining a targeted cell type from tissue when practicing enzymatic dissociation/disaggregation disclosed by the art references of record.
Regarding the 103 rejection over JP’823, Crespo, WO143, Yarmush, Baldan and Grange applicant argues that their surprising results presented are applicable to the rejection.
Applicants results are drawn to a comparison of the cells treated with the claimed composition versus cells without a preservation composition and with those treated with HypoThermosol, which does not comprise albumin or lactate as claimed. Therefore, the surprising results are not deemed to be surprising when comparing treated cells to non-treated cells. The art references teach preservation compositions comprising albumin and lactate as claimed. Therefore, applicants do not demonstrate an unexpected result compared to the prior art compositions.
Additionally, Applicant's arguments do not comply with 37 CFR 1.111(c) because they do not clearly point out the patentable novelty which he or she thinks the claims present in view of the state of the art disclosed by the references cited or the objections made. Further, they do not show how the amendments avoid such references or objections.
Conclusion
THIS ACTION IS MADE FINAL.
Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIFFANY M GOUGH/ Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
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