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 .
Detailed Action
This action is in response to the papers filed August 5, 2025.
Claim Amendments
Applicant’s amendment to the claims filed 08/05/2025 is acknowledged.
Claims 1-155, 157-159, 162-167, 169, 171 and 175 have been cancelled.
Claims 156, 161, and 172 are amended.
Claims 177-187 are newly added.
Claims 156, 160-161, 168, 170, 172-174, 176-187 are pending.
Claims 156, 160-161, 168, 170, 172-174, 176-187 are under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements presently in effect over the instant application:
Applicant elected without traverse the invention of Group I, drawn to a first method for manufacturing tumor-reactive T cells, in the reply filed 02/01/2023. See the Requirement for Restriction/Election mailed 12/23/2022. As previously stated in the Office action mailed 03/13/2023, non-elected Groups II and III (second and third methods) have been rejoined. The restriction requirement between elected Group I (methods) and non-elected Group IV (compositions) is maintained. Election of Group I was made without traverse in the reply filed on 02/01/2023.
Priority
The instant application 17/822,767 was filed on 08/26/2022. This application is a continuation (CON) of international stage application PCT/US2021/020320 filed 03/01/2021, claiming priority based on U.S. Provisional Application 62/982,704 filed 02/27/2020.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 02/05/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Prior rejection under 35 U.S.C. 112(a):
The prior rejection under 35 U.S.C. 112(a) for new matter regarding the limitation a therapeutically effective dose of greater than 1 x 108 CD3+ T cells or viable cells thereof has been withdrawn because, in the most recent reply filed on 08/05/2025, applicant identified where support for the new limitation may be found in the specification as originally filed, which was not previously provided. See page 8 of remarks filed 08/05/2025.
Prior rejections under 35 U.S.C. 102(a)(2):
The prior rejections of the claims under 35 U.S.C. 102(a)(2) as being anticipated by WO 2021/108727 A1 and WO 2020/172202 A1 have been withdrawn because applicant has provided a statement establishing common ownership, thereby invoking the prior art exception under 35 U.S.C. 102(b)(2)(C). In particular, applicant submits that the present application (U.S. Appl. No. 17/822,767) and the subject matter disclosed in the references WO 2021/108727 A1 and WO 2020/172202 A1 were, at the time the invention was effectively filed as of its earliest priority date of February 27, 2020, owned by Myst Therapeutics, Inc. See page 14 of remarks filed 08/05/2025.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 160-161, 168, 177, 181 and 186 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
This rejection is newly applied, necessitated by amendment.
Claim 160, dependent upon claim 156, recites that “the concentration of recombinant IL-2 is between at or about 1000 IU/mL and at or about 6000 IU/mL.” The limitation “the concentration of recombinant IL-2” lacks sufficient antecedent basis because it is unclear if the limitation is referring to the IL-2 concentration in (c)(i) the first expansion step, or (c)(ii) the second expansion step, or both (c)(i) and (c)(ii). For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Similarly, claim 161, dependent upon claim 156, recites that “the concentration of recombinant IL-2 is between at or about 2000 IU/mL and at or about 3000 IU/mL.” The limitation “the concentration of recombinant IL-2” lacks sufficient antecedent basis because it is unclear if the limitation is referring to the IL-2 concentration in (c)(i) the first expansion step, or (c)(ii) the second expansion step, or both (c)(i) and (c)(ii). For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Similarly, claim 168, dependent upon claim 156, recites that “the concentration of IL-15 is from 100 IU/mL to 500 IU/mL.” The limitation “the concentration of IL-15” lacks sufficient antecedent basis because it is unclear if the limitation is referring to the IL-15 concentration in (c)(i) the first expansion step, or (c)(ii) the second expansion step, or both (c)(i) and (c)(ii). For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Similarly, claim 177, dependent claim 156, recites “the anti-CD3 antibody is OKT3.” The limitation “the anti-CD3 antibody” lacks sufficient antecedent basis because it is unclear if the limitation is referring to the anti-CD3 antibody in (c)(i) the first expansion step, or (c)(ii) the second expansion step, or both (c)(i) and (c)(ii). For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Similarly, claim 181, dependent upon claim 180, recites that “the concentration of recombinant IL-2 is from 100 IU/mL to 6000 IU/mL, the concentration of IL-7 is from 100 IU/mL to 2000 IU/mL, the concentration of IL-15 is from 100 IU/mL to 1000 IU/mL, and the concentration of IL-21 is from 0.5 IU/mL to 20 IU/mL.” The limitations “the concentration of recombinant IL-2” and “the concentration of IL-7” and “the concentration of IL-15” and “the concentration of IL-21” each lack sufficient antecedent basis because it is unclear if the limitations are referring to the cytokine concentrations in (c)(i) the first expansion step, or (c)(ii) the second expansion step, or both (c)(i) and (c)(ii). For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Similarly, claim 186, dependent claim 180, recites “the anti-CD3 antibody is OKT3.” The limitation “the anti-CD3 antibody” lacks sufficient antecedent basis because it is unclear if the limitation is referring to the anti-CD3 antibody in (c)(i) the first expansion step, or (c)(ii) the second expansion step, or both (c)(i) and (c)(ii). For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 177 and 186 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
This rejection is newly applied, necessitated by amendment.
Claims 177 and 186 contains the trademark/trade name OKT3™.
As evidence, please see Wagner et al. (2018) “A two-step approach for the design and generation of nanobodies” International journal of molecular sciences, 19(11), 3444, 16 pages: “The FDA approval of the first monoclonal antibody, Orthoclone OKT3™, for clinical use in 1985” (pg. 1).
Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name.
In the present case, the trademark/trade name is used to identify/describe a murine CD3 monoclonal antibody and, accordingly, the identification/description is indefinite.
For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 156, 160-161, 168, 170, 172-174, 176-178, 180-183, 185-187 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/210131 A1 to Chartier-Courtaud et al., of record in IDS filed 08/05/2025; in view of Hinrichs et al. (2014) “Exploiting the curative potential of adoptive T‐cell therapy for cancer” Immunological reviews, 257(1), 56-71, of record; Thommen et al. (2018) "A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade" Nature medicine, 24(7), 994-1004, of record; Tøndell et al. (Jan. 2020) “Ectonucleotidase CD39 and checkpoint signalling receptor programmed death 1 are highly elevated in intratumoral immune cells in non–small-cell lung cancer” Translational oncology, 13(1), 17-24, of record; Gros et al. (2014) “PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors” The Journal of clinical investigation, 124(5), 2246-2259, of record; and Duhen et al. (2018) “Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors” Nature communications, 9:2724, 13 pages.
This rejection is newly applied, necessitated by amendment.
Chartier-Courtaud provides methods for expanding tumor-infiltrating lymphocytes (TILs) and producing therapeutic populations of TILs. See, e.g., Abstract.
The manufacturing process comprises:
(a) producing a single cell suspension processed by homogenization and enzymatic digestion of one or more tumor fragments from a resected tumor of a tumor-bearing subject (see, e.g., par. 5, 379, 384), wherein the tumor fragments comprise CD3+ T cells having CD4 and CD8 positivity (par. 213, 229);
(c)(i) seeding the selected cells into a first culture vessel and expanding the seeded cells for 3-14 days or 7-14 days with one or more T-cell stimulating agents comprising an anti-CD3 antibody and a recombinant cytokine selected from IL-2, IL-7, IL-15, IL-21 or combinations thereof (see, e.g., par. 5, 389, 396, 399-400), wherein the concentration of IL-2 is 1000 IU/mL or 6000 IU/mL (see, e.g., par. 393), the concentration of IL-15 is 100 IU/mL or 500 IU/mL (see, e.g., par. 394), and the concentration of IL-21 is 0.5 IU/mL or 20 IU/mL (see, e.g., par. 395);
(c)(ii) seeding cells from the first expansion into a second culture vessel and expanding the seeded cells for 7-14 days with one or more T-cell stimulating agents comprising an anti-CD3 antibody and a recombinant cytokine selected from IL-2, IL-7, IL-15, IL-21 or combinations thereof (see, e.g., par. 5, 404, 409-411, 413-414), wherein the concentration of IL-2 is 1000 IU/mL or 6000 IU/mL (see, e.g., par. 412), the concentration of IL-15 is 100 IU/mL or 500 IU/mL (see, e.g., par. 416), and the concentration of IL-21 is 0.5 IU/mL or 20 IU/mL (see, e.g., par. 417);
(d) harvesting the population of expanded T cells (see, e.g., par. 5, 213, 522), wherein the number of harvested cells is sufficient to provide a therapeutically effective dose of 1.5 x 109 to 1.5 x 1010 CD3+ T cells for infusion (see, e.g., par. 226; Figure 2); and
(e) formulating the harvested population of expanded T cells as a therapeutic composition for administration to the subject (see, e.g., par. 5, 526-527), wherein the therapeutic composition is formulated with a cryoprotectant (see, e.g., par. 560, 562).
An exemplary workflow, “process 2A,” is also provided in Figure 9:
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Chartier-Courtaud does not disclose a step (b) of selecting cells surface positive for PD-1 and CD39, as instantly claimed.
However, a step (b) of selecting cells surface positive for PD-1 and CD39, as instantly claimed, would have been prima facie obvious over the prior art for the following reasons:
Hinrichs disclosure:
Hinrichs teaches that tumor-reactive T cells can be identified and isolated directly from resected tumors using cell sorting (i.e., cell selection) based on binding to fluorescently labeled antibodies against activation markers (e.g., 4-1BB or other markers), expanded ex vivo, and formulated for reintroduction to the patient (Figure 1B). The process is further described on page 62: “tumor-reactive T cells might be isolated directly from tumor digests using markers of T-cell activation, a strategy that would shorten the time required to produce TIL cell products and that might enable extension of this approach to other types of cancers that have rare but avid tumor-specific populations in their TILs.”
Accordingly, Hinrichs teaches selection of tumor-reactive T cells from resected tumors by sorting cells based on binding of fluorescently labeled antibodies against activation markers, prior to ex vivo expansion, would shorten the time required to produce TIL cell products and enable adoptive transfer for cancer types that have rare but avid tumor-specific population in their TILs.
Hinrichs does not teach the selection of cells surface positive for PD-1 and CD39.
Thommen disclosure:
Thommen discloses the selection of TILs from a resected tumor sample based on PD-1 expression, followed by ex vivo expansion under conditions used for adoptive transfer (Abstract; pg. 996; first page of Methods). Selection of PD-1+ T cells was performed by contacting the cell population with an anti-PD-1 fluorescently-labeled antibody and using a fluorescence-based cell sorter (fig. 1; first page of Methods). The sorted cell population having high PD-1 expression (denoted as PD-1T) an intrinsically high capacity for tumor recognition and strongly predictive for both response and survival in a small cohort of non-small-cell lung cancer patients treated with PD-1 blockade (Abstract). The PD-1T population further showed high expression of mRNA for a wide array of other receptors with known inhibitory function, including CD39 (fig. 3b; pg. 997).
Accordingly, by sorting cells from a resected tumor sample using anti-PD-1 antibodies and using a fluorescence-based cell sorter, Thommen selected for a TIL population surface positive for both PD-1 and CD39, and said selected TIL population was identified as having intrinsically high capacity for tumor recognition (i.e., tumor-reactive).
Tøndell disclosure:
Tøndell discloses the selection of TILs from a resected tumor sample based on PD-1 and CD39 expression (Abstract). Selection was performed by contacting the cell population with anti-CD39 and anti-PD-1 fluorescence-labelled antibodies and sorting using a fluorescence-based cell sorter (pg. 19; fig. 1). Tøndell found that the fraction of CD39+ PD-1+ T cells was “consistently and highly significantly higher” when cells were isolated from a resected tumor as compared to normal tissue (pg. 19; and pg. 21: “[e]xpression of [CD39 and PD-1] was found to be much higher in both CD4+ and CD8+ T cells from tumor than in such cells from adjacent normal lung tissue”).
Accordingly, Tøndell selected for a TIL population surface positive for both PD-1 and CD39 by sorting cells from a resected tumor sample using anti-PD-1 and anti-CD39 antibodies and using a fluorescence-based cell sorter.
Gros disclosure:
Gros, in seeking effective makers to select for tumor-reactive TILs for therapeutic use in adoptive transfer, found that PD-1 expression accurately identifies the repertoire of clonally-expanded, tumor-reactive TILs (Title, Abstract; see also pg. 2250: “selection of PD-1+, LAG-3+, and TIM-3+ CD8+ TILs reproducibly separated the tumor-reactive cells from the non–tumor-reactive cells present in all the fresh tumors tested”). Selection was performed by contacting cells from a resected tumor with fluorescently-conjugated antibodies, including anti-PD-1 antibodies, and using a fluorescence-based cell sorter (pg. 2257). Gros observed that the “overwhelming majority of tumor-reactive cells were derived from cells expressing PD-1” (pg. 2256). The results establish that selecting for CD8+ TILs based on expression of PD-1 and other inhibitory receptors can be used to enrich for the tumor-reactive population, and, although expression of inhibitory receptors may be associated with an exhausted or functionally impaired state, Gros found that the selected TILs expanded in IL-2 were capable of secreting IFN-γ and lyse tumor in vitro, “support[ing] the notion that immune dysfunction associated with coexpression of inhibitory receptors on CD8+ TILs can be reversed, and may enable the reproducible enrichment of tumor-reactive cells for patient treatment” (pg. 2255, last paragraph).
Accordingly, Gros selected for a TIL population surface by contacting cells from a resected tumor sample with anti-PD-1 antibodies and using a fluorescence-based cell sorter, which is a process resulting in selection for cells surface positive for both PD-1 and CD39 (Thommen, above). Expression of PD-1 was found to accurately identify tumor-reactive TIL population, and, following expansion with IL-2, the selected TILs were capable secreting IFN-γ and lyse tumor in vitro, supporting the notion that PD-1 expression may enable the reproducible enrichment of tumor-reactive cells for patient treatment (adoptive transfer).
Duhen disclosure:
Duhen selected TILs from a resected tumor based on expression of CD103 and CD39, and, although the cell population had an exhausted tissue-resident memory (TRM) phenotype, the selected TILs efficiently killed autologous tumor cells following ex vivo expansion (Abstract; fig. 6). Selection was performed by contacting the cell population with anti-CD103 and anti-CD39 antibodies and using a fluorescence-based cell sorter (pg. 11), and the selected CD103+ cells displayed high expression of activation/exhaustion markers, including CD39 and PD-1 (pg. 2; fig. 1b). Duhen concludes that the selected cells “express high levels of exhaustion markers, have a high frequency of tumor-reactive cells, have a distinct TCR repertoire and are capable of recognizing and killing autologous tumor cells” (pg. 2).
Accordingly, by contacting the cell population from a resected tumor with anti-CD103 and anti-CD39 antibodies and using a fluorescence-based cell sorter, Duhen selected for a TIL population surface positive for both PD-1 and CD39. Moreover, although the selected cells displayed high expression of exhaustion markers, including CD39 and PD-1, said cells were tumor-reactive, having a distinct TCR repertoire and capable of recognizing and killing autologous tumor cells.
Motivation to combine:
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the manufacturing process of Chartier-Courtaud to further comprise a step (b) of selecting cells surface positive for PD-1 and CD39, which was found in each of Thommen, Tøndell, Gross and Duhen, with a reasonable expectation of success because selection of tumor-reactive TILs, prior to ex vivo expansion, would shorten the time required to produce TIL cell products and enable adoptive transfer for cancer types that have rare but avid tumor-specific population in their TILs (Hinrichs, fig. 1B; pg. 62), and surface expression of PD-1 and CD39 accurately identifies the tumor-reactive TIL population (Thommen, Abstract; Tøndell, pg. 19, 21; Gross, Abstract, pg. 2255-2256; Duhen, pg. 2, fig. 6).
Claim 180 further recites that step (b) is performed using a fluorescence-based cell sorter, which is taught by Thommen (fig. 1, Methods), Tøndell (pg. 19, fig. 1), Gross (pg. 2257) and Duhen (pg. 11).
Claim 156 further recites that step (b) is performed by contact with antibodies that bind to PD-1 and CD39, which is taught by Tøndell (pg. 19, fig. 1).
For these reasons, both methods of manufacture according to claims 156 and 180 are found to be prima facie obvious over the prior art.
Dependent claims:
Regarding claim 160, Chartier-Courtaud teaches the concentration of IL-2 is 1000 IU/mL or 6000 IU/mL in the first expansion (see, e.g., par. 393) and 1000 IU/mL or 6000 IU/mL in the second expansion (see, e.g., par. 412).
Regarding claim 161, Chartier-Courtaud teaches the concentration of IL-2 is 2000 IU/mL or 4000 IU/mL in the first expansion (see, e.g., par. 393) and 2000 IU/mL or 4000 IU/mL in the second expansion (see, e.g., par. 412).
Regarding claim 168, Chartier-Courtaud teaches the concentration of IL-15 is 100 IU/mL or 500 IU/mL in the first expansion (see, e.g., par. 394) and 100 IU/mL or 500 IU/mL in the second expansion (see, e.g., par. 416).
Regarding claim 170, Chartier-Courtaud teaches the therapeutic composition is formulated with a cryoprotectant (see, e.g., par. 560, 562).
Regarding claims 172 and 182, Chartier-Courtaud teaches the first and second expansion are carried out in a closed system (see, e.g., Abstract, par. 5, 402, 430).
Regarding claims 173 and 183, Chartier-Courtaud teaches the closed system comprises at least one of a gas permeable culture vessel or a bioreactor (see, e.g., par. 5, 402, 409, 422, 430).
Regarding claims 174 and 185, Chartier-Courtaud teaches the tumor is a tumor of melanoma, non-small-cell lung cancer (NSCLC), lung cancer, bladder cancer, cervical cancer, or head and neck cancer (see, e.g., par. 76).
Regarding claim 176, Chartier-Courtaud teaches the therapeutically effective dose is 1.5 x 109 to 1.5 x 1010 CD3+ T cells for infusion (see, e.g., par. 226; Figure 2).
Regarding claims 177 and 186, Chartier-Courtaud teaches that the CD3 antibody is OKT3™ in the first and second expansion (see, e.g., par. 5, 396, 413).
Regarding claims 178 and 187, Chartier-Courtaud teaches that the cells are seeded at a density 1 x 106 cells in 2 mL (par. 390), which is equivalent to 0.5 x 106 cell/mL, or 10-40 x 106 cells in 10-40 mL (par. 397), which fairly suggests 1.0 x 106 cells/mL.
Regarding claim 181, Chartier-Courtaud teaches the concentration of IL-2 is 1000 IU/mL or 6000 IU/mL in the first expansion (see, e.g., par. 393) and in the second expansion (see, e.g., par. 412), the concentration of IL-15 is 100 IU/mL or 500 IU/mL in the first expansion (see, e.g., par. 394) and in the second expansion (see, e.g., par. 416), and the concentration of IL-21 is 0.5 IU/mL or 20 IU/mL in the first expansion (see, e.g., par. 395) and in the second expansion (see, e.g., par. 417).
Chartier-Courtaud does not teach the concentration of IL-7 is from 100 IU/mL to 2000 IU/mL in the first or second expansion, as claimed in claim 181. However, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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). See MPEP 2144.05. In this case, both the methods of manufacture instantly claimed and taught by Chartier-Courtaud are directed to expansion of a TIL population by culturing in the presence of IL-7, and there is no evidence of record that the instantly claimed concentration of IL-7 is critical to the manufacturing process. Moreover, one of ordinary skill in the art would have been motivated to optimize the concentration of IL-7 through routine experimentation in order to improve expansion of the TIL population. For these reasons, the instantly claimed range of 100-2000 IU/mL for IL-7 would have been prima facie obvious over the prior art.
Response to arguments:
As set forth above, applicant’s amendments to the claims have necessitated new grounds of rejection. Applicant’s arguments filed in response to the previous 35 U.S.C. 103 rejections are therefore considered moot or otherwise sufficiently addressed by the new grounds of rejection.
Claims 179 and 184 are rejected under 35 U.S.C. 103 as being unpatentable over Chartier-Courtaud, Hinrichs, Thommen, Tøndell, Gros, and Duhen, as applied to claims 156, 160-161, 168, 170, 172-174, 176-178, 180-183, 185-187 above; in further view of Sadeghi et al. (2011) "Large-scale bioreactor expansion of tumor-infiltrating lymphocytes" Journal of immunological methods, 364(1-2), 94-100, of record.
This rejection is newly applied, necessitated by amendment.
Regarding claims 179 and 184, the claim recites that the first expansion and the second expansion are carried out with perfusion. Chartier-Courtaud does not expressly disclose that the closed system expansion is carried out with perfusion.
Sadeghi discloses the large-scale expansion of TILs with perfusion, where perfusion “allows for higher cell densities and absolute cell numbers as compared to static culture conditions” and provides “a labor- and cost-effective method to reach large numbers of T cells for adoptive cell transfer therapy in the clinic” (Abstract). “Moreover, by using the bioreactor in combination with perfusion, culture media can be exchanged in a continuous manner which improves cell proliferation rates and final yields” (pg. 99).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the manufacturing method of Chartier-Courtaud by carrying out the expansion with perfusion, as taught by Sadeghi, with a reasonable expectation of success because perfusion allows culture media to be exchanged in a continuous manner, improving cell proliferation rates and final yields.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631