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 .
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 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.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on Jun. 27, 2025 has been entered. All arguments and corrected Specification have been fully considered.
Status of the Claims
Claims 18, 19 and 23-25 are currently pending.
Claims 18 and 25 are amended.
Claims 24 and 25 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 1-17, 20-22 and 26 are cancelled.
Claims 18, 19, and 23 have been considered on the merits.
Specification Objections
Specification objections are withdrawn due to amendment.
Claim Objections
New claim objections are added due to amendment.
The disclosure is objected to because of the following informalities:
Claim 18 is objected to because of the following informalities: the first time an acronym is utilized in a claim-set, said acronym should be spelled out in its entirety followed by said acronym in parenthesis (e.g. Dulbecco’s Modified Eagle’s Medium with Ham’s F12 (DMEM/F12)).
Appropriate corrections are appreciated.
Claim Rejections - 35 USC § 112
The claim rejections under 35 USC § 112, (a) or first paragraph (pre-AIA ), are withdrawn due to amendment. New claim rejections under 35 USC § 112, (a) or first paragraph (pre-AIA ) have been added to address the claim amendments.
The claim rejections under 35 USC § 112, (b) or second paragraph (pre-AIA ), are withdrawn due to amendment.
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 18, 19, and 23 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 claims contain 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 pre-AIA the inventors, at the time the application was filed, had possession of the claimed invention.
Claim 18 recites a step/a limitation of :
“wherein the culturing in step (a) and/or (c) is performed using a culture medium composition consisting of:
culture medium, a neuronal cell culture supplement containing progesterone, N2 supplement, human epidermal growth factor, and human fibroblast growth factor;
culture medium, a neuronal cell culture supplement containing progesterone, N2 supplement, human epidermal growth factor, human fibroblast growth factor and Rho-associated protein kinase (ROCK) inhibitor;
culture medium, a neuronal cell culture supplement containing progesterone, N2 supplement, human epidermal growth factor, human fibroblast growth factor and antibiotics; or
culture medium, a neuronal cell culture supplement containing progesterone, N2 supplement, human epidermal growth factor, human fibroblast growth factor, ROCK inhibitor and antibiotics.”
The specification describes the medium composition further containing B27™ Supplement, N2 supplement, EGF, FGF, ROCK inhibitor and antibiotics (0008, 0026, 0036, 0040 and 0043 and Table 1 of published application), but does not describes a neuronal cell culture supplement containing progesterone. There is no description of a neuronal supplement containing progesterone. This appears to be an attempt to describe the B27™ Supplement using the ingredients. However, the B27® Supplement, which has a specific formula, has been instead replaced with a more generic and incomplete list of ingredients. There is no support for the generic list of ingredients in the specification for the B27™ Supplement.
Claims 19 and 23 depend from claim 18 and, therefore claims 19 and 23 contain the new matter and must also be rejected under 35 U.S.C. § 112 (a).
This is a new matter rejection.
Claim Rejections - 35 USC § 103
The claim rejections under 35 USC § 103 are withdrawn due to amendment. New claim rejections under 35 USC § 103 have been added to address the claim amendments.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 18, 19, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (US 2017/0267977 A1) as evidenced by Brewer et al. (Journal of Neuroscience Research, 1993) in view of Sachs et al. (WO 2016/083613 A2) (ref. of record).
With respect to claim 18, Huang teaches a method for culturing a 3-dimensional organoid and where the organoid is a lung cancer organoid (0012, 0022 and 0049-0051). With respect to claim 18 step (a), Huang teaches digesting fresh primary pancreas tumors with collagenase and culturing the cells in 3D culture chambers containing a bed of Matrigel or a biomatrix substance to obtain a cancer organoid (0009 and 0063). With respect to limitation of “removing the cell culture substrate from the lung cancer organoid” of claim 18 step (a) and the “subjecting the obtained organoid to treatment with an enzyme and then allowing the reaction to proceed” of claim 18 step (b), Huang teaches serial passaging of pancreas tumor organoids where the organoids were treated with collagenase and dissociated with trypsin, collecting the cells following the enzyme treatments (0063). This step would readily be understood by one of ordinary skill in the art to remove the cell substrate from the cancer organoid. With respect to claim 18 step (c), Huang teaches reseeding the cells in the 3D culture containing the Matrigel which would be understood to form a cancer organoid (0063).
The method cited in Huang in the example is directed to culturing a pancreas cancer organoid (0063) and Huang does not explicitly teach these steps for culturing lung cancer organoid as recited in claim 18. However, Huang teaches that the methods can be used to culture a 3-dimensional lung cancer organoid (0022 and 0049-0051). Accordingly, at the effect time of filing of the claimed invention, one of ordinary skill in the art, based on the disclosure of Huang that lung cancer organoids can also be cultured using the disclosed methods would have modified the method disclosed in the example to include lung cancer organoids. Since Huang teaches the methods can be used for other cancer organoids, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification.
With respect to the culture media used in steps (a) and (c) of claim 18, Huang teaches a culture medium for culturing the organoids containing a cell culture medium, an antioxidant, a serum free supplement, an insulin receptor agonist, a glucocorticoid and a FGFR agonist (0006 and claim 1). Huang teaches that the culture medium is DMEM-F12 (0036 and claim 4). Huang teaches that the serum-free supplement is B27™ or N2 (neuronal cel culture supplements) (0038 and claim 6). Huang teaches that the antioxidant can be vitamin A which is a component of B27™ as evidenced by Brewer (0037 and claim 5). Huang teaches that the insulin receptor agonist is insulin which is a component of B27® as evidenced by Brewer (0039 and claim 7). Huang teaches that the glucocorticoid is corticosterone which is a component of B27™ as evidenced by Brewer (0040 and claim 8). Brewer report the contents of B27™ Supplement includes biotin, L-carnitine, corticosterone, ethanolamine, D(+)-galactose, glutathione (reduced), linoleic acid, linolenic acid, progesterone, putrescine, retinyl acetate, selenium, T3 (triodo-1-thyronine), DL-α-tocopherol (vitamin E), DL-α-tocopherol acetate, bovine albumin, catalase, insulin, superoxide dismutase, and transferrin (Table 1). Huang teaches that the FGFR agonist is FGF (0041 and claim 9). In addition, Huang teaches that EGF is preferably used when generating lung organoids (0051). Huang teaches the medium further containing an antibiotic (0034 and claim 2).
With respect to claim 19, Huang teaches the cell culture substrate or biomatrix substance is Matrigel® (an extracellular matrix extracted from Engelbreth-Holm-Swarm mouse sarcoma) and is typically proteinaceous such as collagen and laminin (0054). With respect to claim 23, Huang teaches the enzyme is trypsin (0063).
Huang does not teach the medium containing a ROCK inhibitor as recited in claim 18.
However, Sachs reports the successful culturing of primary lung epithelial cells in a medium supplemented with a ROCK inhibitor and teaches the method where the medium contains a ROCK inhibitor (pg. 29 lines 5-12, pg. 43 lines 9-13 and pg. 46 lines 12-24). Sachs teaches that ROCK inhibitors help prevent anoikis, a form of programmed cell death which is induced by anchorage-dependent cells detaching from the surrounding extracellular matrix. Accordingly, at the effect time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to include a ROCK inhibitor in the media used in the method taught by Huang for the benefit of preventing cell death or anoikis as taught by Sachs. It would have been obvious to one of ordinary skill in the art to include additional beneficial components such as a ROCK inhibitor to the cell to the media used in the method taught by Huang, since ROCK inhibitors were known to be included in cell culture media and for the culturing of liver cancer organoids as taught by Sachs. For these same reasons one of ordinary skill would have had a reasonable expectation of success including a ROCK inhibitor in the media used in the method taught by Huang.
Huang does not teach the method where the medium includes both a neural cell culture supplement containing progesterone and a N2 supplement as recited in claim 18.
However, Sachs teaches a culture medium for cancer spheroids include lung cancer organoids that contains both B27™ and N2 supplements (pg. 2 lines 18-19, pg. 33 lines 21-26, pg. 35 line 12, pg. 38 lines 10-15 and pg. 55 lines 8-24). Sachs teaches that supplements such as B27™ and N2 supplements stimulate the proliferation of some cells (pg. 38 lines 10-15). Accordingly, at the effect time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to include both B27™ (a neuronal cell culture supplement containing progesterone) and N2 supplements in the media used in the method taught by Huang for the benefit of promoting proliferation of the cells as taught by Sachs. It would have been obvious to one of ordinary skill in the art to include both supplements in the media used in the method taught by Huang, since both supplements were known to be included in cell culture media and for the culturing of liver cancer organoids as taught by Sachs. For these same reasons one of ordinary skill would have had a reasonable expectation of success include both supplements in the media used in the method taught by Huang.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed Jun. 27, 2025 have been fully considered but they are not persuasive.
With respect to the rejections under 35 U.S.C. § 103, Applicant argues that Sachs teaches a different medium in Example 5 for culturing the lung cancer organoids than the claimed medium and does not teach the method including a culture substrate as claimed or the claimed combination of steps (Remarks pg. 8 last para. to pg. 9 para. 3). Applicant argues that Sachs does not actually teach an additional culturing step and only teaches cellizing (Remarks pg. 9 para. 3). Applicant argues that Sachs discloses a large number of potential components that can be included in an organoid culture medium which would result in a vast number of combination. Accordingly, Applicant argues that from these combinations it would not have been reasonable to expect that the claimed medium composition would be capable of successfully supporting the 3D culture of lung cancer organoids especially since the medium taught by Sachs for culturing lung organoids is material different in composition from the claimed medium (Remarks pg. 9-10 bridging para.). Applicant argues that the medium used in Example 5 of Sachs includes additional components and the claim is limited to only those components listed as defined by the claimed language of “consisting of” (Remarks pg. 10 para. 2). Applicant argues that Sach does not use a culture substrate from culturing the lung cancer organoids in Example 5, and, therefore, does not teach step of (a) of the claimed invention where a substrate is used and subsequently removed prior to enzyme treatment (Remarks pg. 10 last para.). Applicant argues that Noggin is an essential component in Sachs and the present invention enables the successful 3D culture of lung cancer organoids through a combination of technical differences from Sachs including the specific composition of the culture medium the use and removal of a culture substrate in step (a) and the sequential and coordinated implementation of step (s) to (c) (Remarks pg. 11 para. 1). The Applicant’s amendments further limiting the culture medium in claim 18 necessitated the withdrawal of the previous rejection. Applicant’s arguments are drawn in part to Sachs failing to teach the new limitations. However, the new limitations are addressed in the new rejection.
Applicant argues that ThermoFisher does not remedy the deficiencies of Sachs (Remarks pg. 11 para. 3). Applicant’s arguments with respect to ThermoFisher have been considered but are moot because the arguments do not apply to any of the references being used in the current rejection. Furthermore, ThermoFisher was an evidentiary reference supporting the TrypLE™ Express taught by Sachs is a trypsin substitute. ThermoFisher was not a reference supporting a rejection under U.S.C. §103, and thus is not being used to establish obviousness of a particular limitation.
Applicant requests the rejoinder of withdrawn claims 24-25 upon allowance of claim 18 (Remarks. Pg. 11 para. 5). However, the claim 18 remains rejected under 35 U.S.C. §103.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/EMILY A CORDAS/Primary Examiner, Art Unit 1632