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 .
1. Claims 1 -17 are pending.
Election/Restrictions
2. Applicant’s election without traverse of Group I (claims 1 – 7 and 12) in the reply filed on 09/08/2025 is acknowledged.
3. Claims 8 – 11 and 13 – 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 09/08/2025.
4. Claims 1 – 7 and 12 are under consideration.
Priority
5. This application is a National Stage entry of JP2021/019947 filed on 05/26/2021 and claims priority to JP2020-092303 filed on 05/27/2020.
6. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
7. The information disclosure statement (IDS) submitted on 02/21/2023 and 06/27/2024 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
8. The drawings filed on 05/08/2023 are acknowledged.
Specification
9. The use of the term ProNectin, Matrigel, Cell Handler, FACS Aria II, B27, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
10. Claim 1 is objected to because of the following informalities: in line 5, “a combination of at least one selected from the group consisting of” should read “a combination of addition agents where at least one is selected from the group consisting of”. The claim does not recite what is being combined but Applicant’s specification at page 8 para. 0013, states “the culture medium contains 0-10% (v/v) extracellular matrix and addition agents” and defines “addition agents” at page 12, para. 0031 – 0032. Appropriate correction is required.
11. Claim 1 is objected to because of the following informalities: in line 6 – 7, “(HGF); bone morphogenetic protein (BMP) inhibitor; and TGFβ inhibitor” should read “(HGF), bone morphogenetic protein (BMP) inhibitor, and TGFβ inhibitor” where semicolons are replaced with commas. Appropriate correction is required.
12. Claim 6 is objected to because of the following informalities: in line 1 – 2, “wherein the lung epithelial stem cell” should read “wherein the lung epithelial cell” because claim 1 does not recite “lung epithelial stem cell”. Appropriate correction is required.
13. Claim 6 is objected to because of the following informalities: in line 3, “epicelial” should read “epithelial”. Appropriate correction is required.
14. Claim 7 is objected to because the claim references Table A (see MPEP 2173.05(s)). Recitation of Table A in line 3 and inclusion of Table A is not necessary as Applicant’s specification defines each of the recited cell types at page 17 – 18, para. 0055 – 0057. Appropriate correction is required.
15. Claim 12 is objected to because of the following informalities: inline 2, “by a method” should read “by the method”. Appropriate correction is required.
Claim Interpretation
16. For the purpose of applying prior art, claim 1 is interpreted as a combination of addition agents and at least one of the addition agents is selected from KGF, FGF10, HGF, BMP inhibitor and TGFβ inhibitor.
17. For the purpose of applying prior art, claim 7 is interpreted as the lung epithelial stem cell of the sample that is cultured comprises club-I cells or AT2 cells or club-II cells because Applicant’s specification defines “lung epithelial cell” at page 9, para. 0017 to include club cell or AT2 cell.
18. For the purpose of applying prior art, claim 12 is interpreted as an organoid or cells from dissociation of the organoid.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
19. Claim 1 – 7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Instant claim 1 is drawn to a BMP inhibitor and TGFβ inhibitor and instant claim 2 is drawn to an agent capable of activating Wnt signaling, each of which have a wide array of activities and/or effects. Thus the claims are broadly drawn to any compound or molecule which inhibits any factor of the BMP signaling pathway, any factor of TGFβ signaling, and any factor that activates Wnt signaling. Therefore, the claims are considered genus claims that encompass a wide array of compounds. The claims encompass any inhibitor of any BMP, any inhibitor of TGFβ, and any activator of Wnt, which are not described by their function, structure, or relation thereto. The genus for the BMP inhibitor, TGFβ inhibitor, and Wnt activator are highly variant, inclusive to numerous structural variants because a significant number of structural differences between genus members is permitted.
From the specification, it is clear that Applicants have possession of Noggin for the BMP inhibitor, SB431542 for the TGFβ inhibitor, and CHIR99021 for the activator of Wnt signaling (page 29, Table 4; page 30, para. 0116; page 31, Table 5; page 34, para. 0137; page 38, Table 7). However, the claims are not limited to these small molecule compounds. The specification does not disclose a diverse genus. The specification does not place any structure, chemical or functional limitations on the embraced by genus “BMP inhibitor”, “TGFβ inhibitor” or “agent capable of activating Wnt signaling”. The specification instead states that the Wnt signaling agent may be a protein, a GSK-3 inhibitor, or a β-catenin degradation inhibitor; the BMP inhibitor may be a small molecule compound, protein DNA, RNA, siRNA or antisense oligonucleotide; and the TGFβ inhibitor may be a small molecule compound, protein DNA, RNA, siRNA or antisense oligonucleotide (page 13, 0039 – 0042; page 14, 0043). The recitation of “BMP inhibitor”, “TGFβ inhibitor” and “agent capable of activating Wnt signaling” does not convey a common structure or function for each genus and is not so defined in the specification. In sum the specification and the claims do not provide any guidance on the structure of the genus “BMP inhibitor”, the genus “TGFβ inhibitor” or the genus“agent capable of activating Wnt signaling”.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claims are broad generics, with respect to all of the potential species of BMP inhibitors, TGFb inhibitors and Wnt signaling activators that may exhibit one, all, of or any of the claimed activity. The possible variations of compounds are limitless with potentially thousands of compounds that may exhibit the claimed activities. The purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter claimed by them. A patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that the inventor invented the claimed invention. Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention."
The specification lacks sufficient variety of species of compounds to reflect this variance in the genera since the specification does not provide any examples of such genera of compounds. Accordingly, the specification fails to provide adequate written description for the genus of “a BMP inhibitor”, the genus of “a TGFb inhibitor”, and the genus of “an agent capable of activating Wnt signaling” and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed had possession of the entire scope of the claimed invention. Moreover, the specification neither describes the complete structure of a representative number of species, nor describes a representative number of species in terms of partial structure and relevant identifying characteristics. Absent of such teachings and guidance as to the structure and function of these compounds, the specification does not describe the claimed antagonist in such full, clear, concise and exact terms so as to indicate that Applicant had possession of these extracts at the time of filing of the present application. Thus, the written description requirement has not been satisfied.
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.
20. Claim 7 is 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.
21. Regarding claim 7, it is unclear if the lung epithelial cell in the sample is a club-I cell or AT2 cell, or club-II cell, or if the sample comprises the lung epithelial cell or the lung cancer cell and a club-I cell or AT2 cell or club-II cell or if the sample excludes one or all of club-I, AT2, and club-II cells. In other words, it is unclear if claim 7 is further limiting the sample to a lung epithelial cell that is one or all of a club-I, AT2, and club-II cell or excluding the recited cells from the sample. Claim 7 does not recite that the selected cell is cultured.
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.
22. Claim 12 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an organoid derived from a lung epithelial cell and/or lung epithelial cells without significantly more. The claim(s) recite(s) organoid and cells from the organoid which is not shown to be different from that in nature.
The Office published Office's new guidance document entitled 2019 Revised Patent Subject Matter Eligibility Guidance, published January 7, 2019. Applicant is directed to the Federal Register, Volume 4, No. 4, pages 50-57 at page 74621.
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Step 1 of the USPTO' s eligibility analysis entails considering whether the claimed subject matter falls within the four statutory categories of patentable subject matter identified by 35 U.S.C. 101: Process, machine, manufacture, or composition of matter. The claims are directed to a composition of matter (Step 1, Yes).
Step 2A of the 2019 Revised Patent Subject Matter Eligibility Guidance is a two-prong inquiry. In Step 2A Prong One, examiners evaluate whether the claim recites a judicial exception. The composition of matter (organoid or cells from the organoid) is directed to a natural phenomenon (Step 2A, prong 1, Yes). Because claim 12 recites a nature-based product limitation (organoid or cells from the organoid), the markedly different characteristics analysis is used to determine if the nature-based product limitation is a product of nature exception. Applicant’s specification defines “organoid derived from lung epithelial cell” as a biological tissue-like construct, in vitro produced in three dimensions (page 11, para. 0028). The markedly different characteristics analysis is performed by comparing the nature-based product limitation in the claim to its naturally occurring counterpart to determine if it has markedly different characteristics from the counterpart. Here, the closest natural counterpart is naturally occurring lung epithelial cells. When the claimed organoid or cells from the organoid is compared to this counterpart, the comparison indicates that there are no differences in structure, function or other characteristics. McQualter (McQualter, Jonathan L., et al. Proceedings of the National Academy of Sciences 107.4 (2010): 1414-1419), hereinafter McQualter teaches during lung development in the mouse, progenitors of the anterior foregut endoderm undergo directed differentiation to establish distinct respiratory epithelial cell compartments and alveolar epithelial cells make up the gas exchange surface of the alveoli (page 1414, left col. para. 1). McQualter teaches the mouse lung contains a lung epithelial stem cell that gives rise to airway and alveolar epithelial cells (Abstract; page 1414, right col. para. 1 – 2; page 1418, left col. last para.; Figure 6B). Further, the claimed organoid or cells is not markedly different from the natural counterpart as a result of being produced by the method of claim 1 because there is no evidence that the method imbues any markedly different characteristics compared to the natural counterpart and MPEP 2113 (I) states that product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. Therefore, the claimed organoid or cells is a product of nature exception and recites a judicial exception.
In Step 2A Prong Two, examiners evaluate whether the claim recites additional elements that integrate the exception into a practical application of that exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. Besides the judicial exception, the claim recites the judicial exception is “a regenerative medical composition”. An evaluation of whether this limitation is insignificant extra-solution activity is then performed. Note that because Step 2A Prong Two analysis excludes consideration of whether a limitation is well-understood, routine, conventional activity, this evaluation does not take into account whether or not the limitation is well-known. When so evaluated, this additional element is insignificant extra-solution activity because “regenerative medical composition” is recited so generically. The claim does not recite what any components of the composition apart from the judicial exception and is an intended use of the judicial exception. Therefore, “regenerative medical composition” fails to meaningfully limit the claim because it is at best the equivalent of merely adding the words “apply it” to the judicial exception. Accordingly, this element does not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception (Step 2A, prong 2, No).
In Step 2B, the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements adds an inventive concept into the claim. As discussed with respect to Step 2A Prong Two, the claim recites “a regenerative medical composition”, which is at best the equivalent of merely adding the words “apply it” to the judicial exception. Mere instructions to apply an exception cannot provide an inventive concept. At Step 2B, the evaluation of the insignificant extra-solution activity consideration takes into account whether or not the extra-solution activity is well-known. Here, recitation of the organoid or cells from the organoid being in the form of a regenerative medical composition is recited at a high level of generality and does not amount to significantly more and does not provide an 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.
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 claim do not impose limits on the claim scope such that they are not markedly different in structure from a naturally occurring product.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
23. Claim(s) 1 – 7 and 12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nikolic (Nikolić, Marko Z., et al. elife 6 (2017): e26575.), hereinafter Nikolic which is cited on the IDS filed 06/27/2024.
Claim 1 is drawn to A method of producing an organoid derived from a lung epithelial cell or a lung cancer cell, comprising culturing a sample including the lung epithelial cell or the lung cancer cell
in a culture medium, wherein the culture medium contains 0-10% (v/v) extracellular matrix, and
a combination of at least one selected from the group consisting of keratinocyte growth
factor (KGF), fibroblast growth factor (FGF) 10, and hepatocyte growth factor (HGF); bone morphogenetic protein (BMP) inhibitor; and TGF~ inhibitor, and the culture medium is substantially free of feeder cells.
Claim 12 is drawn to a regenerative medical composition comprising an organoid derived
from a lung epithelial cell, produced by a method according to claim 1, and/or cells from
the organoid.
Regarding claim 1, Nikolic teaches a method of producing an organoid comprising culturing lung epithelial tips (“lung epithelial cell”) in a culture medium containing 10% Matrigel (“0 – 10% (v/v) extracellular matrix”) and FGF10, Noggin, CHIR99021, and SB31542 (“a combination of at least one selected from” “FGF10” and BMP inhibitor, “TGFβ inhibitor”) and the culture medium does not contain feeder cells (page 8, last para.; page 9, para. 1; page 19, para. 2; Figure 3).
Regarding claim 2, Nikolic teaches culturing with CHIR99021 (“agent capable of activating Wnt signaling”) (page 9, para. 1).
Regarding claim 3, Nikolic teaches the combination of FGF10, CHIR99021, Noggin, and SB431542 (“FGF10, the agent capable of activating Wnt signaling, the BMP inhibitor, and the TGFβ inhibitor” (page 9, para. 1; page 11, last para.).
Regarding claim 4, Nikolic teaches Noggin and SB431542 (page 9, para. 1).
Regarding claim 5, Nikolic teaches CHIR99021 (page 9, para. 1).
Regarding claim 6, Nikolic teaches a method of producing organoids from tip cells from 19 pcw lungs where tip cells from 19 pcw comprise cells that express Sftpc which is a marker of AT2 cells (“alveolar epithelial cell”) (page 3, para. 2; page 9, para. 3; Figure 1C). Nikolic teaches a method of producing organoids comprising culturing stalk cells in the same medium used to culture lung epithelial tips where the stalk cells comprise cells with basal and club cell markers (page 8, para. 3; page 9, para. 2).
Regarding claim 7, Nikolic teaches selecting lung epithelial tips comprising AT2 cells based on the marker ETV5 and culturing these cells to form organoids (Figure 2J; page 8, para. 2; page 9, para. 1). Nikolic teaches selecting human stalk cells comprising club-II cells based on the marker SCGB3A2 (determined by RNAseq) and culturing these cells to form organoids under the same conditions used for culturing lung epithelial tips (page 6, para. 4; Figure 2K; page 9, para. 2).
Regarding claim 12, Nikolic teaches cells isolated from organoids (“cells from the organoid”) were intra-tracheally transplanted into mice with injured lungs (page 12, para. 3; page 27, para. 2).
Therefore, Nikolic anticipates claims 1 – 7 and 12.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZANNA M BEHARRY whose telephone number is (571)270-0411. The examiner can normally be reached Monday - Friday 8:45 am - 5:45 pm.
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/Z.M.B./Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632