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
The instant application is a national stage entry under 35 U.S.C. § 371 of PCT/JP2021/013465 (filed 03/30/2021). Acknowledgement is made of Applicants’ claim for priority to Japanese Application No. JP2020-062512 (filed 03/31/2020).
Response to Amendment
Applicants’ response filed on 10/23/2025 has been received and entered in the application file.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claim 20 under 35 U.S.C. 112(d):
The cancelation of claim 20 renders the rejection thereof moot.
RE: Rejection of claims 9-12, 14-17, and 19-20 under 35 U.S.C. 101 as directed to a product of nature judicial exception without significantly more:
The cancelation of claims 12, 17, and 19-20 renders the rejections thereof moot.
Claims 9 and 14 have been amended to recite synthetic StemReginin1 (SR1) as the aryl hydrocarbon receptor antagonist; the amendment is sufficient to overcome the remaining rejections of record for claims 9-11 and 14-16.
The rejections are withdrawn.
RE: Rejection of claims 1-4 and 6-20 under 35 U.S.C. 102(a)(1) and (a)(2) over André-Schmutz, et al.:
The cancelation of claims 4, 6, 12-13, and 17-20 renders the rejections thereof moot.
The amendment to claim 1 requiring the CD34+ cell to be a CD34+/CD43-/CD184-/CD73- cell induced from a pluripotent stem cell is sufficient to obviate the rejections of record for claim 1 and its dependent claims.
Therefore, the rejections for claims 1-3 are withdrawn.
Regarding claims 9-11: Claim 9 is drawn to a product, specifically a medium comprising SR1 and IL-3. The remaining limitations recited in independent claim 9 are considered intended use limitations. Intended use limitations only limit the product in so far as the product must be capable of being used as recited. See MPEP 2111.02. In the instant case, and under broadest reasonable interpretation, a medium comprising SR1 and IL-3, as recited in claim 9, is capable of inducing a T cell progenitor from a CD34+/CD43-/CD184-/CD73- cell. André-Schmutz, et al. teaches a method for generating T cell progenitors, comprising culturing CD34+ cells in a medium comprising SR1 and IL-3 (pgs. 11, 20); thus, the medium of André-Schmutz, et al. anticipates the product of claim 9-11.
Therefore, the rejections of record for claims 9-11 are maintained.
Regarding claims 14-16: Claim 14 is drawn to a product, specifically a composition (i.e., the T cell progenitor inducer) comprising SR1 and IL-3. The remaining limitations recited in independent claim 14 are considered intended use limitations. Intended use limitations only limit the product in so far as the product must be capable of being used as recited. See MPEP 2111.02. In the instant case, and under broadest reasonable interpretation, a composition, e.g., a medium, comprising SR1 and IL-3, as recited in claim 14, is capable of inducing a T cell progenitor from a CD34+/CD43-/CD184-/CD73- cell. André-Schmutz, et al. teaches a method for generating T cell progenitors, comprising culturing CD34+ cells in a medium comprising SR1 and IL-3 (pgs. 11, 20); thus, the medium André-Schmutz, et al. anticipates the product of claims 14-16. This is supported by the specification of the instant application: “The T cell progenitor inducer according to the present invention may contain the same ingredients as those of the medium…” (pg. 19, lines 15-16).
Therefore, the rejections of record for claims 14-16 are maintained.
RE: Rejection of claims 1-2, 6-7, 9-10, 13-15, and 18-20 under 35 U.S.C. 102(a)(1) and (a)(2) over Stefanski, et al.:
The cancelation of claims 6, 13, and 18-20 renders the rejections thereof moot.
The amendment to claims 1, 9, and 14 requires the medium and inducer to comprise SR1 and IL-3; as the Stefanski, et al. disclosure does not teach the inclusion of IL-3, the amendment is sufficient to obviate the remaining rejections of record.
The rejections are withdrawn.
RE: Rejection of claim 5 under 35 U.S.C. 103 over André-Schmutz, et al. in view of Ditadi, et al.:
The cancelation of claim 5 renders the rejection thereof moot.
However, as the limitation recited in claim 5 has been incorporated into claim 1, Applicants’ remarks concerning the instant rejection will now be addressed.
Applicants assert André-Schmutz, et al. does not teach or suggest a method or medium comprising an aryl hydrocarbon receptor antagonist and IL-3, much less SR1 and IL-3; further asserting André-Schmutz, et al. does not teach or suggest the use of IL-3 in combination with an aryl hydrocarbon receptor antagonist. Respectfully, this argument is not found persuasive. André-Schmutz, et al. teaches a method for generating T cell progenitors, comprising culturing CD34+ cells in a medium comprising SR1 and IL-3 (pgs. 11, 20).
Applicants further assert a person having ordinary skill in the art would have recognized induced pluripotent stem cell (PSC)-derived CD34+ cells differ significantly from CD34+ hematopoietic stem/progenitor cells (HSPC); respectfully, this argument is not found persuasive.
As evidenced by the Ditadi, et al. disclosure, hematopoietic stem cells (HSCs) develop from a progenitor population known as hemogenic endothelium (HE); HE undergoes an endothelial-to-hematopoietic transition (EHT) to generate blood cell progenitors that mature and give rise to functional HSCs (pg. 580; par. 2); it is also known in the art T cell progenitors arise from HSCs that have traveled from the bone marrow to the thymus, where they reach maturity.
Ditadi, et al. teaches a CD34+, hPSC-derived, definitive HE cell population, which progresses through EHT in a NOTCH-dependent fashion that generates myeloid, erythroid, and lymphoid progeny (pg. 582; par. 1). In these hPSC-derived cells, only the CD73-CD184--derived population underwent EHT and gave rise to T cell progenitors (pg. 588; par. 4); these cells are also CD43- (Fig. 4). Ditadi, et al. further teaches following the NOTCH-dependent EHT, the HE cell population gives rise to CD45+ multipotent progenitors representative of the HSC precursor stage of hematopoietic development (pg. 590; par. 4).
Therefore, as Ditadi, et al. teaches hPSC-derived CD34+/CD43-/CD184-/CD73- cells undergo EHT the way primary T cell progenitors have, and that hPSC-derived HE generates multipotent hematopoietic progenitors that are seemingly the equivalent of HSC precursors (pg. 590; par. 3) and give rise to T cell progenitors (pg. 588; pars. 1, 4), a person having ordinary skill in the art would have recognized the iPSC-derived CD34+/CD43-/CD184-/CD73- cells as functional equivalents to the CD34+ HSPCs of André-Schmutz, et al., and such an individual would have a reasonable expectation of the iPSC-derived cells of Ditadi, et al. responding to cell culture conditions (i.e., differentiation when cultured in a medium comprising SR1 and IL-3) in an equivalent manner as the HSPCs of André-Schmutz, et al.
Lastly, Applicants assert the instant application provides unexpected results of producing engraftable T cell progenitors from CD34+ cells induced from pluripotent stem cells in the presence of an aryl hydrocarbon receptor antagonist and IL-3. Respectfully, this argument is not found persuasive. It is noted that the features upon which Applicants’ argument relies (i.e., T cell progenitors capable of engraftment, wherein the T cell progenitors are obtained from pluripotent stem cell-derived CD34+ cells without the introduction of oncogenes) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Claim Interpretation
The following comments are made to establish broadest reasonable interpretation for the record.
Regarding claims 1, 9, 14: These claims reference a T cell progenitor; as supported in lines 12-16 on pg. 9 of the instant specification, the term T cell progenitor is interpreted as a CD34+CD7+ hematopoietic cell in the process of differentiation from hematopoietic stem cell to CD3+ T cell.
Regarding claim 14-16: These claims are drawn to a T cell progenitor inducer. In the absence of a definition from the specification of the instant application, the term inducer is being interpreted as any molecule that initiates or triggers a cellular process; e.g., a signaling cascade or cellular differentiation.
Maintained Grounds of Rejections
Claim Rejections - 35 USC § 102
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 9-11 and 14-16 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by André-Schmutz, et al. (WO 2018/146297).
André-Schmutz, et al. teaches an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing an antagonist of the aryl hydrocarbon receptor (Abstract).
Regarding claims 9-11, 14-16: André-Schmutz, et al. teaches a medium for culturing CD34+ cells in a method for generating T cell progenitors, wherein the medium comprises aryl hydrocarbon receptor antagonist SR1 (pg. 20; lines 9-12), ), a fibronectin fragment (pg. 21; lines 1-2), a Delta-like 4 ligand (pg. 20; lines 32-33), and IL-3 (pg. 11; lines 16-20); this anticipates the limitations recited in the instant claims.
Modified Grounds of Rejection
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.
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 1-3, 7-11, and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over André-Schmutz, et al. (WO 2018/146297) in view of Ditadi, et al. (Nat Cell Bio. 2015).
The teachings of André-Schmutz, et al. are set forth above.
Claims 9-11 and 14-16 are anticipated by André-Schmutz, et al.
Ditadi, et al. teaches hemogenic endothelium and arterial vascular endothelium as distinct lineages (Abstract).
Regarding claims 1, 7: André-Schmutz, et al. teaches an in vitro method for generating T cell precursors, comprising the step of culturing CD34+ hematopoietic stem/progenitor cells (HSPCs) cells in a medium comprising an antagonist of the aryl hydrocarbon receptor, in particular StemRegenin 1 (SR1) (pg. 20, lines 9-12); further disclosed is an embodiment wherein the medium comprises IL-3 (pg. 11, lines 16-20). This reads on the method for producing a T cell progenitor, comprising step (1) of culturing a CD34+ cell in a medium containing an aryl hydrocarbon receptor antagonist and interleukin-3 (IL-3) limitation recited in claim 1, as well as the wherein the aryl hydrocarbon antagonist is StemRegenin 1 (SR1) limitation recited in claim 7. André-Schmutz, et al. does not teach the CD34+ cell as a CD34+/CD43-/CD184-/CD73- cell induced from a pluripotent stem cell, as required by the remaining limitation recited in claim 1.
However, Ditadi, et al. teaches a pluripotent stem-cell derived CD34+CD43-CD184-CD73- population of cells with multilineage potential (Fig. 7) that gives rise to T cell progenitors (pg. 588; par. 4); this reads on the CD34+/CD43-/CD184-/CD73- cell induced from a pluripotent stem cell limitation recited in claim 1. Ditadi, et al. teaches
It would have been prima facie obvious to have modified the method of André-Schmutz, et al. by substituting the CD34+ HSPCs with the pluripotent stem-cell derived CD34+CD43-CD184-CD73- cells taught by Ditadi, et al. This conclusion of obviousness is based on the ‘substitution rationale’. As Ditadi, et al. teaches the hPSC-derived CD34+CD43-CD184-CD73- cell population progresses through the endothelial-to-hematopoietic transition (pg. 582; par. 1), generates multipotent hematopoietic progenitors equivalent to HSC precursors (pg. 590; par. 3), and gives rise to T cell progenitors (pg. 588; pars. 1, 4), a person having ordinary skill in the art would have recognized the iPSC-derived CD34+/CD43-/CD184-/CD73- cells as functional equivalents to the CD34+ HSPCs of André-Schmutz, et al. Such an individual would have a reasonable expectation of the iPSC-derived cells of Ditadi, et al. responding to cell culture conditions (i.e., differentiation when cultured in a medium comprising SR1 and IL-3) in an equivalent manner as the HSPCs of André-Schmutz, et al.; thus, the use of the pluripotent stem-cell derived CD34+CD43-CD184-CD73- cells in place of the CD34+ HSPCs is a predictable use of prior art elements according to their established functions, leading to the predictable result of the generation of T cell progenitors. This rationale aligns with the principle of a simple substitution of one known element for another to obtain predictable results; see MPEP 2143(I)(B).
This renders obvious the limitations recited in claims 1 and 7.
Regarding claims 2-3: Following the above discussion, André-Schmutz, et al. teaches an embodiment wherein a fibronectin fragment is present in the culture medium (pg. 7, lines 21-22); André-Schmutz, et al. further teaches the cells cultured in the presence of an immobilized Notch ligand, e.g., the soluble domain of the Delta-like 4 ligand (pg. 20, lines 12 and 32-33). This reads on the wherein the medium further contains a fragment of fibronectin and DLL4 limitations recited in claims 2 and 3.
Regarding claim 8: Following the above discussion, André-Schmutz, et al. teaches the CD34+ cells were cultured in 24-well plates or 6-well plates (pg. 25, lines 1-2); this reads on the wherein the culturing is a culture in the absence of a feeder cell limitation recited in claim 8.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHRISTOPHER BABIC can be reached at (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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