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 reply dated 08/28/2026 has been received. Claim 9 is newly added.
Claims 1-8 are pending and 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 2 and 3 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of the amendments to the claims.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.
(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.
The rejection of claim(s) 1-7 under 35 U.S.C. 102a1 as being anticipated by Childs (March 2023; IDS) as evidenced by Rao (Glia. 2015 November ; 63(11): 2040–2057. doi:10.1002/glia.22876) and as evidenced by Childs (Nov 2023, BioRxiv, 6.565830;doi: https://doi.org/10.1101/2023.11.06.565830) is withdrawn in light of Applicant’s arguments and amendments to the claims. Childs taught epithelial-only enteroids derived from fetal epithelium and not intestinal spheroids that have various cells types of hindgut.
The rejection of claim(s) 1-7 under 35 U.S.C. 102a1 as being anticipated by Childs (Nov 2023, BioRxiv, 6.565830;doi: https://doi.org/10.1101/2023.11.06.565830) is withdrawn in light of the Childs declaration dated 08/28/2026 that supports that this reference is Applicant’s own work. .
Claim(s) 1 and 4-7 is/are rejected under 35 U.S.C. 102a1 as being anticipated by McCracken (2011, Nature Protocols, 6(12):1920-1928; IDS) as evidenced by Childs (Nov 2023, BioRxiv, 6.565830;doi: https://doi.org/10.1101/2023.11.06.565830).
The rejection is withdrawn with regard to claims 2-3 as McCracken did not teach inclusion of EREG.
McCracken taught a method of differentiating pluripotent stem cells (iPSCs and ESCs, claim 7) into intestinal tissue comprising multiple steps. The early steps lead to hindgut spheroid tissue. This relates to the preamble of claim 1 that recites "derived from human pluripotent stem cells". McCracken obtains hindgut spheroid tissue differentiated from pluripotent stem cells and cultures it in media comprising DMEM/F12 supplemented with Wnt3a, Rspondin1, noggin (claims 22-23) and EGF. McCracken teaches the method give rises to intestinal tissue, complete with intestinal mesenchyme and epithelium consisting of “all of the major intestinal cell types” (claims 1,4 and 5). McCracken describes the method as directing differentiation of PSCs through stages that mimic embryonic intestinal development, resulting in organoids i) containing an epithelium, of which, more than 90% expresses CDX2 (claim 5), ii) having both secretory and absorptive function, iii) containing all of the intestinal epithelial cell types, and iv) containing a stratified mesenchyme and express markers of smooth muscle. The hindgut spheroid is developed over a period of days, which is at least 10 hours (claim 6). With regard to the markers recited in claim 5, the resulting human intestinal organoids express smooth muscle genes (ACTA2, TAGLN, ACTG2, MYLK) and neuroglial identities (S100B, PLP1, STMN2, ELAVL4), CDH5-expressing endothelial cells, TAGLN expressing smooth muscle cells, networks of TUBB3 and Map2 neuron-like cells as well as PECAM+ endothelial cells (see Childs lines 131-157). By harboring all intestinal cell types, these markers would be inherently expressed.
Applicant argues that McCracken does not teach inclusion of EREG. This argument is persuasive with regard to claims 2-3. Applicant argues that inclusion of EGF led to HIOs lacking organized and differentiated smooth muscle, endothelial cells and neurons. This argument is not persuasive because the claims do not require any level of organization. Further, Childs, presented in the rejection as evidence, teaches that carrying out organoid formation with EGF does result in transient formation of neuron-like and endothelial-like cells. There is no requirement by the claims that the cells be present for any specific duration. Applicant argues that Childs uses EREG and not EGF and thus, shouldn’t be relied upon as supporting McCracken. This argument is not persuasive because Childs is relied upon for the discussion of the his formed in the presence of EGF (see lines 86-107).
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 rejection of claim(s) 1 -3 remain rejected under 35 U.S.C. 103 as being unpatentable over McCracken (2011, Nature Protocols, 6(12):1920-1928; IDS) in view of Childs (March 2023, JCI Insight; IDS) is withdrawn in view of Applicant’s argument of unexpected results that substitution of EGF with EREG led to organized smooth muscle.
Claim(s) 1 and 8 remain rejected under 35 U.S.C. 103 as being unpatentable over McCracken (2014, Nature Protocols, 6(12):1920-1928; IDS) in view of Fujii (2015, Nature Protocols, 10,1474-1485).
This rejection using Childs (November, 2023) and Childs (March, 2023), each as the primary reference is withdrawn given that Applicant has overcome the anticipation rejections using each of these references.
McCracken met the limitations of claim 1 but does not teach genetically engineering the organoid.
However, at the time of filing, other methods of forming intestinal organoids were known and Fujii taught genetic modification of those organoids had been carried out via a variety of methods (PiggyBac and Crispr) to make organoids useful to study gene function in intestinal diseases.
It would have been obvious at the time of filing to genetically modify the intestinal organoids made by McCracken given the teachings of Fujii regarding the usefulness of genetically engineering the organoids to study gene function. One would have been motivated to make such a combination as Fujii taught the use of genetically engineered organoids as a tool to study the role of genes in intestinal diseases. One would have had a reasonable expectation of success in making the combination as it was routine in the art to modify genes in cells in vitro using numerous technologies including PiggyBac transfection and Crispr as taught by Fujii.
Applicant refers to arguments set forth above regarding McCracken. These arguments are not persuasive as set forth above.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7 remain rejected and claim 9 is newly rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claim(s) recite(s) an intestinal organoid which is claimed by characteristics possessed by a intestine in nature. It is noted that the Specification defines “organoid” as “…a 3-dimensional growth of mammalian cells in culture that retains characteristics of the tissue in vivo, e.g. prolonged tissue expansion with proliferation, multilineage differentiation, recapitulation of cellular and tissue ultrastructure, etc.” (page 18, lines 1-4). Claim 1 does recite that the organoid is derived from pluripotent stem cells. However, there is nothing in the claim that differentiates the organoid from intestinal tissue in nature. This judicial exception is not integrated into a practical application because for example, if the claim is directed to a naturally occurring organ with additional generic elements such deriving it from a pluripotent stem cell, which do not add a meaningful limitation to the product because the source of the intestinal organoid does not add a meaningful limitation is nothing more than an attempt to generally link the product of nature to a particular technological environment. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The Office published the guidance document entitled 2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Eligibility Guidance), published December 16, 2014.
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Step 2A has recently been revised to include two prongs (Federal Register / Vol. 84, No. 4 / Monday, January 7, 2019):
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Analysis is as follows:
Step 1: The claim is directed to a composition of matter (intestinal organoid that reads on intestine).
Step 2A – Prong 1: Examiners evaluate whether the claim recites a judicial exception. The composition of matter (an organoid) is directed to a natural phenomenon (Step 2A, prong 1, yes). The claim recites an organoid with characteristic features possessed by an intestine in nature. MPEP §2106.04(b)(I) which shows that isolated DNA, cloned animals are considered natural phenomenon, for example.
Step 2A- Prong 2: Examiners evaluate whether the claim recites additional elements that integrate the exception into a practical application of that exception. This judicial exception is not integrated into a practical application because claims 1-7 do not recite additional elements that integrate the judicial exception into a practical application. Claim 2 adds the growth factor epiregulin but this is known to be part of the natural intestinal environment (Childs, 2022, Development, 149(20):dev200641, 7 pages).
Finally, Step 2B the claim is evaluated as to whether it provides an inventive concept. With no additional elements, there is no inventive concept (Step 2B, No).
Markedly different characteristics can be expressed as the product' s structure, function, and/or other properties. In accordance with this analysis, a product that is purified or isolated, for example, will be eligible when there is a resultant change in characteristics sufficient to show a marked difference from the product' s naturally occurring counterpart. If the claim recites a nature-based product limitation that does not exhibit markedly different characteristics, the claim is directed to a ‘‘product of nature' ' exception (a law of nature or naturally occurring phenomenon), and the claim will require further analysis to determine eligibility based on whether additional elements add significantly more to the exception. It is concluded, here, that the claimed natural products are not markedly different from their natural counterparts as a result of an isolation process.
Based on the guidance, The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to significantly more than the judicial exception itself. Limitations that may be enough to qualify as ‘‘significantly more' ' when recited in a claim with a judicial exception include: Improvements to another technology or technical field; improvements to the functioning of the computer itself; applying the judicial exception with, or by use of, a particular machine; effecting a transformation or reduction of a particular article to a different state or thing; adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application; or other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
Limitations that were found not to be enough to qualify as ‘‘significantly more' ' when recited in a claim with a judicial exception include: Adding the words ‘‘apply it' ' (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer; simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, e.g., a claim to an abstract idea requiring no more than a generic computer to perform generic computer functions that are well-understood, routine and conventional activities previously known to the industry; adding insignificant extrasolution activity to the judicial exception, e.g., mere data gathering in conjunction with a law of nature or abstract idea; or generally linking the use of the judicial exception to a particular technological environment or field of use.
In the instant case, the limitations of the claims do not impose limits on the claim scope such that they are not markedly different in structure from a naturally occurring product. In particular, the claims are directed to a intestinal organoid defined by features possessed by a naturally occurring intestine.
Accordingly, as a whole, based upon an analysis with respect to the claim as a whole, claim(s) 1-7 do not recite something significantly different than a judicial exception. Thus, based upon this analysis, the claims are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
Applicant argues that the claims are not directed to an organoid with characteristic features of an intestine in nature. Applicant has added a culture medium to claim 1. The specification does not appear to set forth a definition of “culture medium” and it can be held that blood is a culture medium. Furthermore, it is also held that culture medium fails to change to tissue in any appreciable way that would add significantly more. Culture media is not transformative. Removal of an intestine from a body and placement into a culture medium does not change the tissue. Applicant argues that the Office has not identified a naturally occurring counterpart having all of the features as recited. Applicant argues the claimed tissue is human made through a controlled differentiation process. In response, Applicant has not pointed out which claimed structural feature is not present in intestine tissue in vivo. The claims require epithelial cells, stromal cells, neural cells, endothelial cells, (organized) smooth muscle cells and ICCC and, culture medium. As set forth above, all of these are present in intestinal tissue in nature.
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 VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
