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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/2/2026 has been entered.
Claims status
Claims 1, 3, 4, 6, 7, 9-12 is/are currently pending and is/are under examination.
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.
Rejection of Claim(s) 1, 3, 4, 6, 7 under 35 U.S.C. 102(a)(1) as being anticipated by Kodani et al (JP 2018011527 A, Published 2018/01/25; Machine translation provided in IDS dated 7/8/2024; ref of record) as evidenced by Suga et al (Nature, 2011; ref of record) and Zimmer et al (Stem Cell Reports, Vol. 6, 858–872, June 14, 2016; IDS dated 7/8/2024; ref of record) is withdrawn in favor of the rejection below.
Claim(s) 1, 4, 6, 7 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Nakano (US 12,485,147 B2, Publication Dec 2, 2025; EFD Nov. 24 2017 to JP2017-226312; also published as WO2019/103129 on May 31, 2019).
Regarding claim 1, Nakano discloses a method for producing and separating pituitary hormone-producing cells (col. 1, last para; col. 6, [53]; col. 45, lines 1-40). In Nakano’s method the pituitary hormone-producing cells are derived in vitro from pluripotent stem cells (Example 1, 9) wherein the method results in formation of a cell mass (=claimed aggregate) containing pituitary placode or Rathke’s pouch as required by claim 7, precursors of adenohypophysis, and hypothalamic neuroepithelial tissue that contains neurons which are terminally differentiated cells and have thus inherently lost self-renewal potential (Figure 1-2; Figure 10; col. 6, [55]; col. 20, lines 4-10; col. 43, lines 40-60). Nakano discloses separating pituitary hormone-producing cells from their cell mass by detaching using tweezers (= claimed shredding or physically incising required by claim 4) and collecting (=claimed separating) the outer layer of the cell mass that comprises the pituitary tissue (col. 45, lines 25-40). Nakano also discloses that the outer layer of the cell mass expresses EpCAM (Figure 1-2, 10) and that EpCAM is a marker for non-neural epithelial tissue that forms the pituitary tissue in their cell mass (col. 6, [59, 60]; col. 7, [66]; col. 43, lines 63-67; col. 44, lines 57-60). Nakano shows overlapping expression between EpCAM, Cytokeratin (another non-neural epithelium marker) and markers for precursors of pituitary glands Pitx1, Emx2, Lhx3 (Rathke’s pouch marker) (Figure 1-2, 10). Thus, Nakano discloses separating EpCAM expressing non-neural epithelial tissue that forms the pituitary tissue from their cell mass.
Regarding claim 6, Nakano discloses PSC as hiPSC (Example 9, Figure 10).
Therefore, Nakano anticipates the claimed method.
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.
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.
Rejection of Claim(s) 9-12 under 35 U.S.C. 103 as being unpatentable over et al Kodani et al (JP 2018011527 A, Published 2018/01/25; Machine translation provided in IDS dated 7/8/2024; ref of record) as evidenced by Suga et al (Nature, 2011; ref of record), and in view of Zimmer et al (Stem Cell Reports, Vol. 6, 858–872, June 14, 2016; IDS dated 7/8/2024; ref of record) is withdrawn in favor of rejection below.
Rejection Claim(s) 1, 3, 4, 6, 7, 9-12 under 35 U.S.C. 103 as being unpatentable over Zimmer et al (Stem Cell Reports, Vol. 6, 858–872, June 14, 2016; IDS dated 7/8/2024; ref of record) in view of Kodani et al (JP 2018011527 A, Published 2018/01/25; Machine translation provided in IDS dated 7/8/2024; ref of record) is withdrawn in favor of rejection below.
Claim(s) 3, 9-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nakano in view of Kodani et al (JP 2018011527 A, Published 2018/01/25; Machine translation provided in IDS dated 7/8/2024; ref of record).
Nakano is directed to a method for producing and separating pituitary hormone-producing cells (col. 1, last para; col. 6, [53]; col. 45, lines 1-40). In Nakano’s method the pituitary hormone-producing cells are derived in vitro from pluripotent stem cells (Example 1, 9) wherein the method results in formation of a cell mass (=claimed aggregate) containing pituitary placode or Rathke’s pouch, precursors of adenohypophysis, and hypothalamic neuroepithelial tissue that contains neurons which are terminally differentiated cells and have thus inherently lost self-renewal potential (Figure 1-2; Figure 10; col. 6, [55]; col. 20, lines 4-10; col. 43, lines 40-60).
Regarding claims 3, 9, Nakano teaches separating pituitary hormone-producing cells from their cell mass by detaching using tweezers (= claimed shredding or physically incising required by claim 11) and then collecting (=claimed separating) the outer layer of the cell mass that comprises the pituitary tissue (col. 45, lines 25-40). Nakano also teaches that the outer layer of the cell mass expresses EpCAM (Figure 1-2, 10) and that EpCAM is a marker for non-neural epithelial tissue that forms the pituitary tissue in their cell mass (col. 6, [59, 60]; col. 7, [66]; col. 43, lines 63-67; col. 44, lines 57-60). Nakano shows overlapping expression between EpCAM, Cytokeratin (another non-neural epithelium marker) and markers for precursors of pituitary gland Pitx1, Emx2, Lhx3 (Rathke’s pouch marker) (Figure 1-2, 10). Thus, Nakano teaches separating EpCAM expressing non-neural epithelial tissue that forms the pituitary tissue from their cell mass.
Nakano also teaches that their pituitary hormone-producing cells are one of GH, PRL, ACTH, TSH, FSH, LH producing cells (col. 7, [67]; col. 21, lines 43-55; col. 21-22, bridge para; col. 41, lines 39-50;) and express at least ACTH and PRL (Example 2, Figure 2) (as required by claim 12).
Nakano does not teach a further step of dispersing the collected outer layer of the cell mass that comprises the pituitary tissue that expresses EpCAM, as recited in claim 3, 9(A,B), and reaggregating the dispersed cells, as recited in claim 9(C), 10.
However, such methods for dispersing cell mass for reaggregation for further culture were known in the art.
Kodani teaches a method of dispersion of cell mass, selection based on cell-surface markers and reaggregation of selected cells for further culture. Kodani teaches dispersing a cell mass using Accumax followed by pipetting to break up the cell aggregate into single cells (as required by claims 3, 9-step(A), Example 1; [0051, 0157]). Kodani teaches separating cells labeled with cell-surface markers such as EpCAM (Example 1, [0158], Figure 12, 16; as required by claim 9-step (B)). Kodani also teaches that selected cells after separation can be reaggregated for subsequence culture [0161, 0162] (as required for claim 9-step (C), claim 10) .
Therefore, it would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to further disperse Nakano’s cell mass that comprises the EpCAM expressing cells using Kodani’s method. An ordinary artisan would be motivated to collect and reaggregate the EpCAM expressing cells produced by Nakano because Nakano teaches that EpCAM is a marker for non-neural epithelial tissue that forms the pituitary tissue in their cell mass and that its expression overlaps with markers for precursors of pituitary glands Pitx1, Emx2, Lhx3 (Rathke’s pouch marker) (Figure 1-2, 10). An ordinary artisan would reasonably expect to collect and reaggregate the EpCAM expressing cells produced by Nakano because methods to collect and reaggregate cells using cell surface marker expression were taught by in Kodani. Further, both Nakano and Kodani teach EpCAM antibodies required for such a method (col. 48, line 14 in Nakano; [155] in Kodani).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
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.
Claim 1, 3, 6, 7, 9-10, 12 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14, 22, 24 of copending Application No. 18/696,610 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claims 1, 9 are directed to a method for separating/producing pituitary hormone producing cells by separating EpCAM expressing cells from a cell aggregate comprising adenohypophysis or its precursor. The cell aggregate comprising adenohypophysis or its precursor comprises hypothalamic neuroepithelial tissue (instant claim 2) and precursors of adenohypophysis such a pituitary placode and Rathke’s pouch (instant claim 7). The cell aggregate comprising adenohypophysis or its precursor is derived from hiPSC (instant claim 6). The step of separation is preceded by a dispersion of cell aggregate step (instant claim 3, 9-step A). Finally, the separated cells are reaggregated in an aggregate or sheet form (instant claim 9-C, 10). The separated/produced pituitary hormone producing cells comprise at least one of the pituitary hormone producing cell types recited in instant claim 12.
The method claims in `610 are not patentably distinct from the instant claims because:
Claims 2, 8 of `610 are directed to a method for separating/producing pituitary hormone producing cells by separating EpCAM expressing cells from a cell aggregate comprising adenohypophysis or its precursor (same as instant claims 1, 9). The cell aggregate comprising adenohypophysis or its precursor are known to comprise hypothalamic neuroepithelial tissue (rendered obvious by claims 1, 7 of `610) and precursors of adenohypophysis such a pituitary placode and Rathke’s pouch (rendered obvious by claims 6 of `610; required for instant claim 7). The cell aggregate comprising adenohypophysis or its precursor could be derived from iPSC and use of human species is obvious to an ordinary artisan to derive human pituitary hormone producing cells (rendered obvious by claims 5 of `610; required for instant claim 6). Dispersion of cell aggregate prior to separation is taught in claims 3, 11, 22 of `610 (required for instant claim 3, 9-step A). Finally, reaggregation of the separated cells is taught in claims 9, 10 of `610 and that the produced cell could be in aggregate or cell sheet form is taught in claim 14 of `610 (required for instant claim 9-C, 10). The separated/produced pituitary hormone producing cells comprise at least one of the pituitary hormone producing cell types recited in instant claim 12 (taught in claim 13, 24 of ‘610).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 4, 11 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14, 22, 24 of copending Application No. 18/696,610 in view of Kodani.
Instant claim 4 and 11 require the dispersion steps of claim 1, 9 to be performed by shredding or physical incision. As detailed in the DP rejection above, Claims 2, 8, 3, 11, 9, 10, 14 of `610 teach instant claims 1 and 9. Specifically, dispersion of cell aggregate prior to separation is taught in claims 3, 11, 22 of `610 (required for instant claim 3, 9-step A). `610 does not teach that the dispersion could be performed by shredding or physical incision. Kodani teaches dispersion of cell aggregate using Accumax followed by pipetting to break up the cell aggregate (= shredding, Example 1; [0051, 0157]). Therefore, it would be obvious to an ordinary artisan to perform the dispersion step taught by `610 using method taught by Kodani. Such a combination would not require inventive ingenuity.
This is a provisional nonstatutory double patenting rejection.
Claim 1, 3, 6, 7, 9-10, 12 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 7, 8, 9, 13, 16, 18, 19 of copending Application No. 18/697,382 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claims 1, 9 are directed to a method for separating/producing pituitary hormone producing cells by separating EpCAM expressing cells from a cell aggregate comprising adenohypophysis or its precursor. The cell aggregate comprising adenohypophysis or its precursor comprises hypothalamic neuroepithelial tissue and precursors of adenohypophysis such a pituitary placode and Rathke’s pouch (instant claim 7). The cell aggregate comprising adenohypophysis or its precursor is derived from hiPSC (instant claim 6). The step of separation is preceded by a dispersion of cell aggregate step (instant claim 3, 9-step A). Finally, the separated cells are reaggregated in an aggregate or sheet form (instant claim 9-C, 10). The separated/produced pituitary hormone producing cells comprise at least one of the pituitary hormone producing cell types recited in instant claim 12.
The method claims in `382 are not patentably distinct from the instant claims because:
Claims 7 of ‘382 are directed to a method for separating/producing pituitary hormone producing cells by separating EpCAM expressing cells from a cell aggregate comprising adenohypophysis or its precursor (same as instant claims 1, 9). The cell aggregate comprising adenohypophysis or its precursor comprises hypothalamic neuroepithelial tissue (claim 7 of `382) and pituitary placode and Rathke’s pouch are known precursors of adenohypophysis (rendered obvious by claim 7 of `382; required for instant claim 7). The cell aggregate comprising adenohypophysis or its precursor is derived from IPSC and use of human species is obvious to an ordinary artisan to derive human pituitary hormone producing cells (rendered obvious by claims 7 of `382; required for instant claim 6). Dispersion of cell aggregate prior to separation is taught in claims 8 of `382 (required for instant claim 3, 9-step A). Finally, reaggregation of the separated cells using suspension culture is taught in claims 7, 13 of `610 and that the produced cell could be in aggregate form is taught in claim 1, 16 of `382 (required for instant claim 9-C, 10). The separated/produced pituitary hormone producing cells comprise at least one of the pituitary hormone producing cell types recited in instant claim 12 (taught in claim 16, 18, 19 of ‘382).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 4, 11 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 7, 8, 9, 13, 16, 18, 19 of copending Application No. 18/697,382 in view of Kodani.
Instant claim 4 and 11 require the dispersion steps of claim 1, 9 to be performed by shredding or physical incision. As detailed in the DP rejection above, Claims 7, 8, 16 of `382 teach instant claims 1 and 9. Specifically, dispersion of cell aggregate prior to separation is taught in claims 8 of `382 (required for instant claim 3, 9-step A). `382 does not teach that the dispersion could be performed by shredding or physical incision. Kodani teaches dispersion of cell aggregate using Accumax followed by pipetting to break up the cell aggregate (= shredding, Example 1; [0051, 0157]). Therefore, it would be obvious to an ordinary artisan to perform the dispersion step taught by `382 using method taught by Kodani. Such a combination would not require inventive ingenuity.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s arguments filed 4/2/2026 regarding the U.S.C. 102 rejection of claims 1, 3, 4, 6, 7 as anticipated by Kodani (pages 5-9) have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant’s arguments filed 4/2/2026 regarding the U.S.C. 103 rejection of claims 9-12 as obvious by Kodani in view of Zimmer (pages 10-12) have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant’s arguments filed 4/2/2026 regarding the U.S.C. 103 rejection of claims 1, 3, 4, 6, 7, 9-12 as obvious by Zimmer in view of Kodani (pages 12-14) have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant's arguments filed 4/2/2026 with respect to the Double Patenting rejections have been fully considered but they are not persuasive. Applicant’s request that the rejection be held in abeyance is acknowledged (page 14, last para). Rejection is maintained.
Conclusion
No claim is allowed.
Relevant prior art made of record but not relied upon for the instant rejections:
Gleiberman et al (Genetic approaches identify adult pituitary stem cells. PNAS, Vol. 105, No. 17, 2008) that teaches EpCAM as a known epithelial marker that also marks pituitary stem cells in not only in embryonic tissue but also adult tissue (i.e. comprising terminally differentiated neurons) in vivo (Figure 1).
Nakano (WO2019/103129; May 31, 2019) and its machine translation is also provided.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATASHA DHAR whose telephone number is (571)272-1680. The examiner can normally be reached M-F 8am-4pm (EST).
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/MATASHA DHAR/Examiner, Art Unit 1632
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