DETAILED ACTION
Notice of Pre-AIA or AIA Status
The text of those sections of Title 35, U.S. Code not included in this action can
be found in a prior Office action.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to the papers filed on 06/10/2026. Claims 1, 3-5, 7, 8, 11 and 12 are currently pending as per claims filed on 06/10/2026. Claims 2 and 6 are cancelled and Claim 1 and 5 have been amended by Applicants’ amendment filed on 06/10/2026.
Applicant’s election with traverse of Group 1, claims 1-6 in the
reply filed on 01/06/2026 was previously acknowledged.
Claim 7, 8, 11, and 12 were previously withdrawn from further consideration by Applicants pursuant to 37 CFR 1.142(b), as being drawn to a nonelected subject invention, there being no allowable generic or linking claim.
Therefore, claims 1 and 3-5 are under examination to which the following grounds of rejection are applicable. Claim 1 is an independent claim.
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.
Withdrawn objections/rejection in response to Applicants’ arguments or Amendment
Claim Rejections - 35 USC § 101
The amendments combined with applicants’ arguments are sufficient to overcome the rejection, therefore the rejection has been withdrawn. The applicant’s amendments further clarify the claimed method is directed to preparing a lung cancer organoid model.
Claim Rejections - 35 USC § 112 (b)
In view of Applicants’ amendment of claim 5, the claim rejection has been withdrawn.
Claim Rejections - 35 USC § 112 (a)
The amendments combined with applicants’ arguments are sufficient to overcome the rejection. Applicant has amended the claim to specifically recite that the method of preparing a lung cancer model comprises fusing normal lung organoids and cancer cells, rather than co-culturing and cancer cells are specifically lung cancer cells. Furthermore, applicant’s arguments have established that undue experimentation is not necessary (page 6-7, Applicant’s Remarks). In view of these amendments and arguments, the rejection has been withdrawn.
New objections/rejection in response to Applicants’ arguments or Amendment
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 and 4 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3, which depends on claim 1, recites the cancer cells are human primary cancer cells or established cancer cells. However, claim 1 recites "lung cancer cells" and claim 3's recitation of are human primary cancer cells or established cancer cells includes cells which are not lung cancer cells, therefore failing to further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 4, which depends on claim 1 and 3, recites a group of established cancer cell lines species. However, claim 1 recites "lung cancer cells" and claim 4's recitation of a group of established cancer cell lines include cell lines which are not lung cancer cells, therefore failing to further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112 (a)
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.
Claims 1 and 3-5 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.
Due to applicants' amendment, the main issues that lead to a rejection under 35 USC 112, first paragraph for lack of enablement have been overcome. The remaining issue cited here is more properly a rejection under 35 USC 112, first paragraph for lack of written description. The previous inclusion in the enablement rejection was due to a number inoperable embodiments that made the ability to perform the invention unpredictable. Applicants' amendment has not overcome the basis of the following rejection.
M.P.E.P. § 2163 recites, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number
of species by actual reduction to practice (see i)(A), above), reduction to drawings (see
i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or
other physical and/or chemical properties, by functional characteristics coupled with a
known or disclosed correlation between function and structure, or by a combination of
such identifying characteristics, sufficient to show the applicant was in possession of the
claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.”
Further, the written description inquiry is limited to that which is contained within the four corners of the specification, not the extent to which the skilled artisan, given his or her
knowledge of the art, would have considered it to expand with only routine
experimentation. See Ariad Pharms. Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010) (en banc); see also id. at 1352 (“[I]t is the specification itself that must
demonstrate possession A description that merely renders the invention obvious does
not satisfy the requirement.").
Claim 1 is directed to a method of preparing a genus of lung cancer models using a normal lung organoid, comprising mixing a normal lung organoid and any lung cancer cell.
The disclosure lacks sufficient description of the genus of methods of preparing any lung cancer model with any normal lung organoid and any lung cancer cells at any ratio. Rather, the disclosure provides description of preparing a H1299 lung cancer model by mixing normal lung organoids and H1299 cancer cells at a ratio of one lung organoid to one hundred H1299 cells and the mixture is centrifuged causing cells to come in close contact and, subsequently, the lung organoid and cancer cells were cultured until the H1299 cancer cells were fused to the organoid (page 15-16, Example 2.). The specification discloses that the resulting lung cancer model comprising H1299 cancer cells expresses alveolar cells and lung fibroblast markers HT1-56, HT2-280, and Col1a1, thus indicating generation of a lung cancer model. Thus, the specification only teaches a method for preparing a H1299 lung cancer model comprising mixing a normal lung organoid and H1299 lung cancer cells. This single lung cancer model does not demonstrate sufficient disclosure such that a person of skill in the art would recognize that applicants were in possession of the full genus of methods and lung cancer models as claimed.
The specification does not disclose that any other lung cancer cell could be used or at any other ratio of organoid to cells in the claimed method for preparing a lung cancer model, and furthermore that any other lung cancer cell type or ratio is suffice to indicate generation of any other lung cancer model other than H1299 lung cancer models.
The prior art indicates different lung cell cancer lines demonstrate different cell physiology, hence suggesting variation in the behavior of lung cancer cells when cultured with organoids. Korrodi-Gregório demonstrated that two lung cancer cell lines, A549 and SW900, exhibit functional proteomic differences which are related to cancer transformation, proliferation, migration, invasion and metastasis (calgizzarin, Rab11a, Rab5c and SLC3A2 in adenocarcinoma cell line and matrin 3, stathmin, vimentin, calcyclin and galectin 1 in squamous carcinoma cell line) (page 19), all of which are characteristics that can influence the in vitro generation of 3-dimensional models using cancer cells and organoids. For this reason, there is no indication that the structure of any lung cancer cell type would elicit the function of generating any lung cancer model with the steps recited in the present invention.
Applicant were referred to the guidelines for Written Description Requirement
published January 5, 2001 in the Federal Register, Vol.66, No.4, pp.1099-1110 (see
http://www.uspto.gov). The disclosure of a single species is rarely, if ever, sufficient to
describe a broad genus, particularly when the specification fails to describe the features
of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue
Pharma L. P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000). The possession may
be shown by actual reduction to practice, clear depiction of the invention in a detailed
drawing, or by describing the invention with sufficient relevant identifying characteristics
(as it relates to the claimed invention as a whole) such that a person skilled in the art
would recognize that the inventor had possession of the claimed invention. See, e.g.,
Pfaff v. WellsElectronics, Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,
1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai
Pharmaceutical, 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991).
The “written description” requirement may be satisfied by using such descriptive
means as words, structures, figures, diagrams, formulas, etc., that fully set forth the
claimed invention. See Noelle v. Lederman, 355 F.3d 1343, 1349, 69 USPQ2d 1508,
1514 (Fed. Cir. 2004) and Lockwood v. American Airlines, Inc., 107 F.3d at 1572, 41
U.S.P.Q.2d at 1966. A definition by function alone “does not suffice” to sufficiently describe a coding sequence “because it is only an indication of what the gene does,
rather than what it is.” Regents of the University of California v. Eli Lilly & Co., 119 F.3 at
1568, 43 USPQ2d at 1406 (Fed. Cir. 1997) (discussing Amgen Inc. v. Chugai
Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d 1016 (Fed. Cir. 1991)). In Fiers v.
Ravel, 984 F.2d at 1169-71, 25 U.S.P.Q.2d at 1605-06 (1993), the CAFC found that “a
mere wish or plan for obtaining the claimed chemical invention” is not sufficient to
describe a chemical invention (discussed in Eli Lilly at 1404).
In view of the vast number of structural variants (i.e. lung cancer cells in claim 1, genus of cancer cells in claim 4, and various ratios of organoid to cell number) encompassed by the claims and the lack of adequate description of the structure-function relationship of the claimed genus in view of the teachings of the prior art, one of ordinary skill in the art would not have recognized Applicant as being in possession of the claimed genus. The limited disclosure in the specification is not deemed sufficient to reasonably convey to one skilled in the art that the applicants were in possessions of the genera of combinations of lung cancer cells and normal lung organoids recited in the claims at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genera.
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.
Claim(s) 1 and 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over
Chakrabarti et al (JoVE, 2021, pages 1-13) and further in view of Zhang et al (PLOS one, 2018, pages 1-8), Msustapha ((National Yang Ming Chiao Tung University, 2022, pages 1-76), and Kang et al (Adv. Healthcare Mater. 2021, pages 1-18).
Chakrabarti teaches a method of preparing human-derived autologous gastric cancer organoid/immune cell co-culture models which can be used to test targeted cancer therapies, the method comprising generating patient-derived gastric organoids and mixing with cytotoxic T lymphocytes (CTLs) wherein the CTLs adhere to the gastric organoids and fuse (page 6-7, right col, 5. Establishing organoid/immune cell co-cultures; Figure 3 showing adhered CTLs to gastric organoids upon culturing).
While Chakrabarti does not teach the method is for producing lung cancer models and centrifuging the mixed normal lung organoid and lung cancer cells, one of ordinary skill in the art would have considered the teachings of Msustapha, Zhang, and Kang as these references are analogous prior art pertaining to using normal lung organoids and lung cancer cell lines to model lung cancer pathophysiology in relation to drug screening and applying centrifugation in 3D cell culture.
Msustapha teaches a method of preparing 3D lung organoid models for studying lung adenocarcinoma tumor microenvironment comprising culturing normal lung bud tip organoids (i.e. a distal lung (alveolar) organoid (page 19, para 2)) in conditioned medium from lung cancer cells (page 14-15, 3.21 Co-culture model).
Zhang teaches methods of generating H1299 cancer cell-derived tumor spheroids as 3D models for drug screening (page 2, 2.2 3D cell culture; page 3, 2.5 Drug treatment) and, compared with 2D models, the 3D models can better represent the real interaction between drugs and cancer tissues (page 6, para 4).
Kang teaches centrifuge-based 3D cell culture systems have the advantage of being able to rapidly promote high-density cell aggregation (i.e. adhering cells in 3D structure) (page 6, left col, para 1).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of mixing normal cells with a cancer organoid and subsequently culturing to produce a cancer model for testing cancer therapies as taught by Chakrabarti to instead use normal lung organoids that are mixed with lung cancer cells to generate a lung cancer model for testing cancer therapies as Msustapha teaches that normal lung organoids can be cultured and furthermore with conditioned media from lung cancer cells for modeling cancer’s effects and Zhang teaches that the lung cancer cell line H1299 can be used to generate 3D organoid/spheroids to also screen cancer therapies. Furthermore, the art of Kang teaches that that centrifugation of cells to form aggregates in 3D cell culture systems (i.e. an organoid which is 3D structure) is widely implemented, thus one would combine the teachings of mixing normal lung organoids with lung cancer cells from Msustapha, Zhang, and Chakrabarti and centrifugation to adhere the cells as a 3D structure. One would be motivated to do so to generate a lung cancer model system for the testing of cancer therapeutics that can better represent the real interaction between drugs and cancer tissues. Since use of H1299 cancer cells for 3D spheroid/organoid production and centrifugation to form spheroids is known in the art, one would have a reasonable expectation of success.
Regarding claim 3 and 4, the teachings of Chakrabarti, Msustapha, Zhang, and Kang render obvious claim 1. Moreover, Zhang teaches the spheroids comprise the established cancer cell line H1299.
Regarding claim 5, the teachings of Chakrabarti, Msustapha, Zhang, and Kang render obvious claim 1. Moreover, Chakrabarti teaches the cells to organoid ratio is 50,000 cells per 200 organoids (i.e. 1 organoid : 250 cells).
Conclusion
No claims are allowed.
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.
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/JULIANA IRENE CANDELARIA/Examiner, Art Unit 1634
/MARIA MARVICH/Primary Examiner, Art Unit 1634
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