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 .
Election/Restrictions
This action is in response to the papers filed on 01/06/2026. Claims 1-8, 11, and 12 are currently pending as per claims filed on 01/06/2026. Claims 9 and 10 have been canceled by Applicants’ amendment filed on 09/19/2023.
Applicant's election with traverse of Group 1, claims 1-6, in the reply filed on 01/06/2026 is acknowledged. Applicant timely traversed the election requirement in the reply filed on 01/06/2026.
Response to Applicants' arguments in relation to restriction requirements.
Applicant’s traversal arguments are essentially that the lung cancer model of Group II requires the method of Group I and that the lung cancer model has features that can only be realized by the method of making of Group I. Moreover, applicant argues that Group III (method of using the lung organoid model) necessitates the same lung cancer model from Group II which requires the method of Group I, thus there is technical unity of Groups I-III. The applicant additionally amended claim 11 such that Group III would require the same lung cancer model derived from the method of making of Group 1.These arguments have been fully considered and not found persuasive.
Groups I, II, and III are directed to a product (lung cancer model), method of using the product (screening a candidate material), and method of making the product which are related to distinct inventions. The invention of Group II (claims 7-8) is a product by process claim. In contrast to Applicants’ remarks, there is not requirement that the lung cancer model of claim 7 requires expression of type 1 and type 2 alveolar cell markers (HTl-56 and HT2-280); and (ii) expression of a lung fibroblast marker (CollAl). Therefore, these markers do not further limit the structure of the claimed lung cancer model of claim 7. Therefore, the lung cancer model (product) of Group II does not reflect the manufacturing method of Group I. Furthermore, the references that would be applied to a product made would not necessarily anticipate or render obvious a method of making a product. Moreover, the literature search, particularly relevant in this art, is not co-extensive and is much more important in evaluating the burden of search. Burden in examining materially different groups having materially different issues also exists. Clearly different searches and issues are involved with each group involving the need to search different classes/subclasses or electronic resources, or employing different search queries, and/or the different inventions raising different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
In relation to the restriction requirement between the methods of Group I and III, and despite the amendment of claim 11, examiner finds that the method of Group III comprises different steps from the method of Group I. Moreover, in relation to the restriction of Group II and III, the method of Group III can be practiced using a materially different product in addition to the product of Group II. Furthermore, the rationale for restricting Groups is explained in the 11/07/2025 requirement for restriction office action. This restriction does pose a search burden to the examiner. The method claims of Groups I and III would be subject to rejoinder if product (used in the methods) claims are found allowable. Note however, that Applicant’s elected invention is directed to a method and not a product.
Claims 7, 8, 11, and 12 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected groups of inventions, there being no allowable generic or linking claim. Reinstatement of claims drawn to non-elected inventions will be withdrawn during prosecution.
The requirement is still deemed proper and is therefore made FINAL.
Please note that after a final requirement for restriction, the Applicants, in addition to making any response due on the remainder of the action, may petition the Commissioner to review the requirement. Petition may be deferred until after final action on or allowance of claims to the invention elected, but must be filed not later than appeal. A petition will not be considered if reconsideration of the requirement was not requested. (See § 1.181.).
Therefore, claims 1-6 are currently under examination to which the following grounds of rejection are applicable.
Priority
This Application claims benefit of foreign filed applications KR 10-2023-0069304 and KR 10-2022-0078899. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) to KR 10-2023-0069304 filed on 05/30/2023 and KR 10-2022-0078899 filed on 06/28/2022.
Filing of certified untranslated copies of the applications KR 10-2023-0069304 filed 09/24/2023 and KR 10-2022-0078899 filed 09/24/2023 is acknowledged.
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
Thus, the earliest possible priority for the instant application is 06/28/2022
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.
Claim 1-6 is rejected under 35 U.S.C. 101 because the claimed invention is not supported by either a well-established or disclosed specific and substantial credible utility. For a utility to be "well-established" it must be specific, substantial and credible.
The instant specification asserts that the lung cancer model, which is made by a normal lung organoid comprising co-culturing a normal lung organoid with cancer cells, can be used to observe the progression or metastasis pattern of lung cancer and for comparing the effect of anticancer agents at stages of progression (page 17, line 1-5). Moreover, the specification asserts that the lung cancer model can be used to study the effect of an anti-cancer agent on both cancer cells and normal cells of the organoid (page 17, line 6-9). The specification asserts that using this lung cancer organoid model avoids the unpredictable reaction caused by using mouse models with injected human cells (page 17, line 10-12).
These above-asserted utilities (functions) of the lung cancer model however are not considered to be a substantial utility because the disclosure does not provide working examples or evidence of the lung cancer model being used for any of the aforementioned functions. Rather, the disclosure only describes potential uses, but there is lack of evidence that these uses can be accomplished with the lung cancer model generated by the claimed method invention. Use of lung cancer organoid models, wherein the model comprises a cancer organoid lacking normal cells, for drug testing is known and has well-described functions (Kim et al 2019, Nature Communications, page 1-15) however, use of a normal organoid with cancer cells as a model has not been shown to have valuable use. Furthermore, the use of a genus of cancer cells with a normal lung organoid, as recited in claims 1 and 2, are not supported by the disclosure. Determining whether the lung cancer model is appropriate and capable of performing the function of studying lung cancer progression and/or testing anticancer agents, let alone by using any of the species of cancer cell types the instant application claims, would require further research by one of ordinary skill in the art. Indeed, one of ordinary skill in the art would also need comparative controls, which are lacking in the specification, to determine if the lung cancer model is properly functioning.
Therefore, since the applicant has not disclosed functional use of the claimed invention, applicant’s claimed invention is incomplete. The current disclosure is therefore deemed lack of specific and substantial utility or well-established utility.
Claim 1-6 is also rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. Specifically, because the claimed invention is not supported by either a substantial or specific asserted utility or a well-established utility for the reasons set forth above, one skilled in the art clearly would not know how to use the claimed invention.
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.
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.
Claim 1-10 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The specification does not reasonably provide enablement for claims directed to:
A method of preparing a lung cancer model using a normal lung organoid, comprising: co-culturing a normal lung organoid and cancer cells, wherein the cancer is one or more selected from the genus of cancers with a contemplated therapeutic utility.
The specification does not enable any person skilled in the art to which it pertains or with which it is most nearly connected, to use the invention commensurate in scope with this claim. Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
the breadth of the claims; the nature of the invention:
The claims are directed to a method of preparing a lung cancer model using a normal lung organoid comprising co-culturing a normal lung organoid and cancer cells with the contemplated function of observing the progression or metastasis pattern of lung cancer and for comparing the effect of anticancer agents at stages of progression (page 17, line 1-5).. The claims are further directed to cancer cells that are selected from a genus of many different cancer types, can be from human primary cells or established cancer cells. Similarly, the established cancer cells are selected from a genus of many difference cancer cell lines.
the amount of direction provided by the inventor; the existence of working examples:
While the specification discloses a reduction to practice of preparing the lung cancer organoid model by preparing the lung organoid and adding H1299 lung cancer cells to the lung organoid (example 1 and 2, page 15-16), it does not reduce to practice methods to perform the co-culture step or any examples of ways in which to use the lung cancer model to test for progression or metastasis pattern of lung cancer and for comparing the effect of anticancer agents at stages of progression (page 17, line 1-5). Rather, the specification discloses that the lung organoid and cancer cells “fuse”, but there is no indication of how to culture the organoids and lung cancer cells such that they are “co-cultured” over a period of time. The specification and drawings only recite days 1, 3, and 7 post-fusion (page 16, line 9; Fig 1-3) and show characteristics observed in lung organoids (example 3, page 16; Figure 4), but do not indicate their ability to successfully model lung function, let alone be used to test anticancer agents or study lung cancer progression, as suggested in the specification (page 16, line 24-25; page 17, line 1-2). Hence, there is no demonstration that the lung cancer model can be used for the purpose as described in the specification. There is no minimal or maximal physiological or phenotypic result which would necessarily tell a skilled artisan the lung cancer model would be appropriate to use for the aforementioned downstream applications.
the state of the prior art; the level of predictability in the art:
The prior art of Kim et al 2019 (Nature Communications, page 1-15) teaches a method of preparing normal and lung cancer organoids, separately, as in vitro models that recapitulate the tissue architecture and cellular components of their respective entity. Moreover, Kim teaches the use of these models for predicting patient-specific therapeutic responses of anti-cancer drugs (Figure 6) and as a method of testing new targeted drugs (page 10, right col, para 1). However, they do not teach the method of generation of normal organoids that are co-cultured with cancer cells. Rather, Kim teaches that “outgrowth of normal organoids is an important cause of failure during cultivation of cancer organoids using an optimal medium for normal organoids” (page 11, right col, para 1). Therefore, the success of co-culturing normal organoids with cancer cells, as is described in the instant application, would be unpredictable because culture conditions for optimally growing lung cancer organoids also causes overgrowth of normal tissue, hence Kim describes two distinct culture medias are required to grow normal and lung cancer organoids separately. Likewise, Sachs et al 2019 (The EMBO Journal, pages 1-20) teaches that normal organoids must be manually removed from lung cancer organoids or must be selected against using Nutlin-3a (page 12, right col, step 6) and have “observed that remnants of normal epithelium in carcinoma samples will rapidly overgrow tumor tissue”, further reiterating that co-culture of normal cells (i.e. healthy organoids) with cancer cells would not be predicted to be successful. Therefore, in view of the teachings of Sachs and Kim, current systems for using a lung cancer organoid model recite the need to eliminate normal organoids/cells in order to generate a functional lung cancer organoid model. In regards to the genus of cancer and cancer cell types recited in instant claim 2-4, the current literature fails to demonstrate the ability to co-culture any of the cancer cell types listed in the instant application with normal lung organoids, additionally demonstrating lack of predictability of success with the claimed method of this instant application.
the quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The skilled artisan would be required to perform undue experimentation in order to practice the claimed invention. The instant specification does not reduce to practice the claimed invention; the instant specification does not provide guidance on how to reasonably predict if the lung cancer model would be appropriate to use for downstream studies such as testing anti-cancer agents or studying lung cancer progression. Moreover, the specification does not reduce to practice the use of any cancer cell line other than H1299, nor does it reduce to practice the process of the “co-culture” with a normal lung organoid. Thus, the skilled artisan would be forced to 1) determine if the generated lung cancer organoid model is sufficient for downstream use and 2) if any cancer cell type other than H1299 would correctly fuse to the normal lung organoid, and 3) how to execute the process of co-culturing.
the level of one of ordinary skill:
The level of one of ordinary skill is a PhD holder.
Conclusion
When all of the Wands factors are considered together, they establish a prima facie case that the specification is not enabling for the claims. The specification only provides details for a method of preparing lung cancer model using a normal organoid comprising “fusing” of a normal lung organoid and H1299 cancer cells and assessing expression of characteristic markers of lung organoids, but not the process of “co-culturing” the lung cancer model.
While a lack of a working embodiment cannot be a sole factor in determining
enablement, the lack of any working examples, in light of the unpredictable nature of the
art and the lack of direction applicants present, provides additional weight to the lack of
enablement in consideration of the Wands factors as a whole. Thus, one of ordinary skill
in the art would not have had a reasonable expectation of success in making or using the claimed invention.
Claims 2, 5 and 6 are 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 applicant regards as the invention.
Claim 2 recites the limitation "cancer" in line 4. There is insufficient antecedent basis for the recitation of “cancer” in the claim. Claim 1 recites “cancer cells” in line 3. Appropriate correction is requested.
Claim 5 recites the limitation "the lung organoid" in line 1. There is insufficient antecedent basis for the recitation of “the lung organoid” in the claim. Claim 1 recites “normal lung organoid” in line 1 and 3. Appropriate correction is requested.
Claim 6 recites the limitation "the mixture" in line 5. There is insufficient antecedent basis for the recitation of “the mixture” in the claim. Appropriate correction is requested.
Note that the Specification defines the term “normal” in paragraph [0041] of the published application as “a non-malignant tumor or a negative state for malignancy, and includes a perfectly normal state without a disease, and a state corresponding to a diseased state other than a malignant tumor (cancer).”
Conclusion
Claims 1-6 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliana Candelaria whose telephone number is (571)272-5488. The examiner can normally be reached Monday - Friday 8am - 5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIANA IRENE CANDELARIA/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634