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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/20/2025 has been entered.
Claims 1 and 4 have been amended. Claims 1 and 3-7 are pending and under consideration.
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, 4 and 6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for does not reasonably provide enablement for a process of screening chemotherapeutics for use in second line chemotherapy comprising subjecting the plural second chemotherapeutic agents and comprising subjecting the first and second chemotherapeutic agents to a liver organoid treatment prior to adding to the culture of the cells of interest, for does not reasonably provide enablement for a process of screening chemotherapeutics for use in second line chemotherapy comprising subjecting the plural second chemotherapeutic agents and comprising subjecting the first and second chemotherapeutic agents to a generic organoid treatment prior to adding to the culture of the cells of interest.. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims..
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re wands, 858 F.2d 731, 737.8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Claims 1, 4 and 6 are broadly drawn to encompass the treatment of each chemotherapeutic agent to generic organoid treatments, such as treatment with colon (Fuji et al, Cell Stem Cell, 2016, Vol. 18, pp. 827-838), pancreas (Balak et al, Current Diabetes Reports, 2019, Vol. 19 , article160, 10 pages), and mammary gland (Sachs et al, Cell, 2018, Vol. 172, pp. 373-386). Skardal et al (WO2018/027023, cited in the prior action) teach that the metabolic activity of the liver can heavily influence the outcome and efficacy of drugs (page 42, lines 2-6 under the heading of “organoid integrated drug screening”). There are no teachings in the specification or any art of record to support the use of an organoid treatment of drugs prior to a screen of chemotherapeutic agents wherein the organoids were not liver organoids One of skill in the art would be subject to undue experimentation in order to carry out the broadly claimed methods with generic organoids.
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 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.
Claims 1, 3, 4-7 are rejected under 35 U.S.C. 103 as being unpatentable over Sengupta (IN2012ko00574, cited in the prior action) in view of Skardal et al (WO2018/027023, cited in the prior action), Mori et al (Oncogene, 2009, Vol. 28, pp. 2796-2805) and Shi et al (WO03/02512).
Sengupta teaches a method comprising preparing a cancer cell suspension obtained from a human cancer patient; forming a monolayer culture in a 96-well plate from the cells, wherein the tumor cells are layered on top of normal cells(Step 3, bridging paragraph, pages 12-13). Sengupta teaches exposing wells to seven different individual chemotherapeutic agents in triplicate (Step 5, pages 13-14), Sengupta discloses that after 48 hours of incubation with the drugs, the medium including dead, detached and/or apoptotic cells is removed, and the remaining cells are fixed and counted to determine the best drug for first line chemotherapy (steps 7 and 8, pages 14-15), which meets the limitation of determining a first chemotherapeutic agent that is the most effective among plural candidate chemotherapeutic agents.
Sengupta does not teach that the plurality of first chemotherapeutic agents have been exposed to a liver organoid treatment, collection of a plurality of non-adhering cancer cells that survived exposure to the most effective first chemotherapeutic agent to prepare plural second cultures, culturing of the non-adhering cancer cells and exposure of each of the second cultures to one or a plurality of second chemotherapeutic agents wherein the plurality of second chemotherapeutic agents have been subject to a second liver organoid treatment; and identification of the most effective member of the plurality of second chemotherapeutic agents.
Skardal et al teach that the metabolic activity of the liver can heavily influence the outcome and efficacy of some drugs (page 42, lines 2-6 under the heading “organoid integrated drug screening”). Skardal et al teach a method of screening a compound of interest comprising circulating a growth medium from a liver organoid to a tumor cell organoid, administering a compound of interest to the liver organoid, and determining the decrease of tumor cells relative to no administration of the compound (page 18, lines 1-9 of the first full paragraph).
Mori et al teach that an anchorage-independent cell growth signature identifies tumors with metastatic potential (title). Mori et al teach that cultured cancer cells exhibit anchorage-independent cell growth which is connected with tumor cell aggressiveness in vivo and metastatic potential (page 2796, second column, lines 4-9 of the middle paragraph). Mori et al teach that analysis of the phenotype of primary breast, ling, ovarian and melanoma tumors indicates that the expression profiling reflects the actual ability of the cells to metastasize in vivo (pages 2801-2802, bridging paragraph).
Shi et al teach that approximately 50% of the patients with local breast cancer who are primarily diagnosed eventually relapse with the metastasis (page 33, lines 3-5).
It would have been prima facie obvious at the time prior to the effective filing date to include liver organoid treatment of the seven different individual chemotherapeutic agents of Sengupta as first chemotherapeutic agents prior to cell treatment and to also include liver organoid treatment of the each of the plurality of second chemotherapeutic agents prior to treatment of the non-adherent cells . One of skill in the art would be motivated to integrate the liver organoid into the screening process for determining a first and second chemotherapeutic agent because Skardal et al teach that metabolism in the liver can heavily influence the outcome and efficacy of some drugs. One of skill in the art would understand that drugs requiring activation by the liver for activity would not be identified in the screen without the liver organoid.
Regarding the requirement for culture of the non-adhering cells surviving the first chemotherapy, Mori et al teach cells which have metastatic potential; are present in the culture of primary cancer cells of various types. Thus, one of skill in the art would be motivated to collect cells having metastatic potential which survived treatment by the first line chemotherapy agent. One of skill in the art would understand that the cells with metastatic potential would exhibit anchorage-independent cell growth and thus be easily detached from the semi-sold medium by rinsing the adherent cells. One of skill in the art would understand that the anchorage independent cells with metastatic ability would be responsible for the relapse of the patient after first line chemotherapy as taught by Shi et al and that it would be desirous to identify the drug which would be effective against the surviving cells having metastatic ability.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 3-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/612,978 in view of Skardal et al (WO2018/027023, cited in the prior action) and Mori et al (Oncogene, 2009, Vol. 28, pp. 2796-2805).
Claim 1 of the ‘978 application teaches the limitations of instant claims 1 and 3-7 with the exception that the claim does not dictate use of the most effective member of the set of plural second chemotherapeutic agents in second-line therapy; subjecting the plural first and second agents to liver organoid treatment; or collecting a plurality of non-adhering cancer cells that survived exposure to the most effective first chemotherapeutic agent to prepare plural second cultures.
Skardal et al teach that the metabolic activity of the liver can heavily influence the outcome and efficacy of some drugs (page 42, lines 2-6 under the heading “organoid integrated drug screening”). Skardal et al teach a method of screening a compound of interest comprising circulating a growth medium from a liver organoid to a tumor cell organoid, administering a compound of interest to the liver organoid, and determining the decrease of tumor cells relative to no administration of the compound (page 18, lines 1-9 of the first full paragraph).
Mori et al teach that an anchorage-independent cell growth signature identifies tumors with metastatic potential (title). Mori et al teach that cultured cancer cells exhibit anchorage-independent cell growth which is connected with tumor cell aggressiveness in vivo and metastatic potential (page 2796, second column, lines 4-9 of the middle paragraph). Mori et al teach that analysis of the phenotype of primary breast, ling, ovarian and melanoma tumors indicates that the expression profiling reflects the actual ability of the cells to metastasize in vivo (pages 2801-2802, bridging paragraph). .
It would have been prima facie obvious at the time prior to the effective filing date to include liver organoid treatment of the individual first chemotherapeutic agents prior to cell treatment and to also include liver organoid treatment of the each of the plurality of second chemotherapeutic agents prior to treatment of the non-adherent cells . One of skill in the art would be motivated to integrate the liver organoid into the screening process for determining a first and second chemotherapeutic agent because Skardal et al teach that metabolism in the liver can heavily influence the outcome and efficacy of some drugs. One of skill in the art would understand that drugs requiring activation by the liver for activity would not be identified in the screen without the liver organoid.
Regarding the requirement for culture of the non-adhering cells surviving the first chemotherapy, Mori et al teach cells which have metastatic potential; are present in the culture of primary cancer cells of various types. Thus, one of skill in the art would be motivated to collect cells having metastatic potential which survived treatment by the first line chemotherapy agent. One of skill in the art would understand that the cells with metastatic potential would exhibit anchorage-independent cell growth and thus be easily detached from the semi-sold medium by rinsing the adherent cells. One of skill in the art would understand that the anchorage independent cells with metastatic ability would be responsible for the relapse of the patient after first line chemotherapy and that it would be desirous to identify the drug which would be effective against the surviving cells having metastatic ability.
This is a provisional nonstatutory double patenting rejection.
All other rejections and/or objections as set forth in the prior action are withdrawn in light f applicant’s amendment of claims 1 and 4.
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643