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 reply dated 7/28/2026 has been received.
Election/Restrictions
Applicant’s election without traverse of group I, claims 20-28 in the reply filed on 03/24/2026 is acknowledged.
Claims 29-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/24/2026.
Clam 20 has been amended and claims 20-28 are under consideration.
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.
The rejection of claims 20-28 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in light of the amendments to the claims.
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.
The rejection of claim(s) 20-28 under 35 U.S.C. 102a1 as being anticipated by Childs (2023, JCI Insight; IDS) is withdrawn as Childs cultured intestinal enteroids formed from fetal crypt tissue and did not culture hindgut spheroid tissue as is required by the claims.
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.
Claim(s) 20-27 remain rejected under 35 U.S.C. 103 as being unpatentable over McCracken (2014, Nature Protocols, 6(12):1920-1928; IDS) in view of Childs (2023, JCI Insight; IDS).
Applicants arguemtns that there wold not have been a reasonable expectation of success in substituting epiregulin for EGF in the methods of McCarcken are not persuasive for reasons set forth below. However, the rejection is withdrawn based on the unexpected functional results as outlined in the Remarks at pages 12-13.
For completeness of the record, Applicant’s aRemarks concerning a reasonable expectation of success in the combination of references meeting the limitations of claims 20-27, are not persuasive.
Applicant addresses the rejection by discussing Childs as though it is the primary references used as the basis of the rejection. McCracken is the primary reference and teaches the claimed method but uses EGF instead of epiregulin to differentiate and maintain the organoid. EREG is an EGF family member that Childs teaches more effectively mimics the in vivo environment in the in vitro development of intestinal tissue.
Applicant argues the Childs adds epiregulin to the culture of epithelial-only enteroid cultures which are distinct from the hindgut spheroids and there would be no motivation to apply the epiregulin used on enteroids to spheroids. In response, while enteroids and spheroids are made of different types of intestinal cells, epiregulin and EGF are proteins of the same family that each bind to the EGF receptor. Childs taught that epiregulin was superior in signaling in intestinal tissue and led to a more open chromatin structure in cells that more closely reflected that of intestinal cells in vivo (Childs, 8). Childs concluded that use of epiregulin in place of EGF provides more physiological conditions in intestinal differentiation (Childs, 10). Thus, the combination of teachings is a substitution as opposed to a replacement with an unrelated molecule.
Childs found epiregulin was highly expressed in the intestinal crypt. EGF and epiregulin are signaling molecules which Childs discusses are expressed by stem cells in intestinal epithelium and signal to the subepithelial compartment. Thus, while Childs discusses epiregulin as being expressed in intestinal epithelial enteroids, it is a signaling molecule that signals other intestinal compartments. Applicant continues by discussing that a POSITA would not have had a reasonable expectation of success in substituting EREG for EGF in hindgut spheroid culture because neither Childs nor McCracken suggest EREG signaling would occur in the mesenchymal components that develop in the claimed hindgut spheroid. In response, epiregulin is an EGF family member that binds the EGF receptor. Epiregulin was found to be beneficial in intestinal development of enteroids when substituted for EGF. Because EGF is also required for differentiation of hindgut spheroids, it would follow that the EGF receptor is expressed on cells of the spheroids and it would be reasonable to expect epiregulin would be a successful substitute for EGF since Childs taught that epiregulin more effectively mimicked the in vivo intestinal environment.
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.
Th rejection of claims 20-24,26-28 remain rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1,11,20,22-23 of copending Application No. 17/549028. An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical but an examined application is not patentably distinct from the reference claims because the examined claim is either anticipate by, or would have been obvious over, the reference claims. See, e.e., 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). Although the conflicting claims are not identical, they are not patentably distinct from each other because claim 20 is generic to all that is recited in claim 1 of USSN 17549028. That is, claim 1 ‘028 falls entirely within the scope of claim 20 of the instant application. Specifically, claim 1 of ‘028 is drawn to the same method of generating intestinal organoids only the ‘028 claims recite culture with 2 EGF family members, EREG and NRG1, while the instant claims are drawn to culture with just EREG. Reference claim 1 also recites inclusion of an agent for activating Wnt, which is recited in pending claims 22 and 23. The instant claim 20 recites 2 culture steps but they are culture with the same media and thus are wholly the same as the single culture step in ‘028. ‘028 claim 1 requires the absence of EGF, which is recited in instant claim 24. Culture for at least 10 hours, claim 26, is standard in the art where culture is usually at least overnight. The concentration recited in claim 21 is also recited in ‘028 claim 23. R-spondin and noggin of claim 23 is recited in copending claim 11. The recited organoid characteristics in claims 27-28 are inherent to the claimed method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant argues that one would not have been motivated to omit NRG1 from the culturing protocol of the ‘028 application. In response, the instant claims do not require NRG1 not be present and the copending claims, in combination, anticipate all limitations of pending claim 20.
Claim 25 remains provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/549028 in view of Childs (2023, JCI Insight; IDS). Claim 1 of ‘028 renders obvious independent claim 20 as set forth above. Instant claim 25 recites that the media does not contain NRG1 while copending claim 1 requires its use. It is held that it would be obvious to carry out the method without NRG1 because Childs taught that EREG, without NRG1 was sufficient to generate spatially organized organoids in vitro.
This is a provisional nonstatutory double patenting rejection.
Applicant does not appear to have addressed this provisional rejection.
Claim 20-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/012,368 in view of Childs (2023, JCI Insight; IDS). Claim 1 through step a of ‘368 is essentially the same as that of dependent claims 22 and 23 with exception that it uses EGF in place of the EREG of pending claim 20. Substitution of EGF with EREG is made obvious by Childs. The “at least 10 hours” of pending claim 26 is an embodiment of copending claim 3.
Childs taught forming intestinal organoids from fetal enteroid tissue explants, using the same culture medium (DMEM/F12 with Wnt3a, R-spondin1 and noggin) supplemented with either EGF (same media as McCracken) or with EREG (1,10 or 100ng/mL claim 21, as claimed). Childs teaches EREG as an EGF family member that is robustly expressed in developing intestinal crypts. Childs states, “Our results demonstrate that EREG can replace EGF in vitro…” (abstract) and “By replacing the EGF ligand with EREG in enteroid growth media, we observed that enteroids derived from the developing human intestine grew in spatially organized crypt-like and villus-like domains, with the full complement of epithelial cell types found in the native intestine, including rare cell populations… (page2, para 2).
It would have been obvious at the time of filing to carry out the method of ‘368 to differentiate intestinal organoids from pluripotent stem cells, substituting EGF with EREG as taught by Childs to arrive at the invention as claimed. One would have been motivated to make such a substitution because Childs compared otherwise identical intestinal spheroid differentiation protocols, differing only in the presence of EGF versus EREG, and found that EREG more accurately mimics the in vivo niche and leads to organoids that more faithfully model the native intestinal epithelium (page 2, para 2, last sentence).
This is a provisional nonstatutory double patenting rejection.
Applicant presents the same arguments with regard to application of Childs in this provisional rejection as they did for the obviousness rejection above. These arguments were not persuasive for reasons discussed above. The obviousness rejection was withdrawn in view of unexpected results, which does not excuse overlapping or timewise-extended claims between commonly owned related patents
Claim 20-28 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of US 12,188,051 in view of Childs (2023, JCI Insight; IDS). Claim 1 through step a of ‘051 is essentially the same as that of dependent claims 22 and 23 with exception that it uses EGF in place of the EREG of pending claim 20. Substitution of EGF with EREG is made obvious by Childs. The “at least 10 hours” of pending claim 26 is an embodiment patent claim 2.
Childs taught forming intestinal organoids from fetal enteroid tissue explants, using the same culture medium (DMEM/F12 with Wnt3a, R-spondin1 and noggin) supplemented with either EGF (same media as McCracken) or with EREG (1,10 or 100ng/mL claim 21, as claimed). Childs teaches EREG as an EGF family member that is robustly expressed in developing intestinal crypts. Childs states, “Our results demonstrate that EREG can replace EGF in vitro…” (abstract) and “By replacing the EGF ligand with EREG in enteroid growth media, we observed that enteroids derived from the developing human intestine grew in spatially organized crypt-like and villus-like domains, with the full complement of epithelial cell types found in the native intestine, including rare cell populations… (page2, para 2).
It would have been obvious at the time of filing to carry out the method of ‘051 to differentiate intestinal organoids from pluripotent stem cells, substituting EGF with EREG as taught by Childs to arrive at the invention as claimed. One would have been motivated to make such a substitution because Childs compared otherwise identical intestinal spheroid differentiation protocols, differing only in the presence of EGF versus EREG, and found that EREG more accurately mimics the in vivo niche and leads to organoids that more faithfully model the native intestinal epithelium (page 2, para 2, last sentence).
Applicant presents the same arguments with regard to application of Childs in this provisional rejection as they did for the obviousness rejection above. These arguments were not persuasive for reasons discussed above. The obviousness rejection was withdrawn in view of unexpected results, which does not excuse overlapping or timewise-extended claims between commonly owned related patents
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 VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
Prosecution Insights