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 .
Claim 3 and 7 have been canceled. Claims 1, 4 and 6 have been amended. Claims 1, 4-6 are pending and under consideration.
The rejection of claims 1, 4 and 6 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for scope of enablement is withdrawn in light of applicant’s amendments of claims 1 and 4 to specify that the organoid treatment was a liver organoid.
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 5 is 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 5 state that the organoid treatment is the treatment with liver organoids. Claim 1 has been amended to require subjecting the first chemotherapeutic agent to a liver organoid. Thus, claim 5 fails to further modify 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.
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.
The rejection of claims 1, 4-6 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) is maintained for reasons of record.
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.
Applicant argues that none of the requirements of “collecting a plurality of non-adhering cancer cells”, “culturing the plurality of non-adhering cancer cells” and using the most effective member in second-line chemotherapy” are found in any of the cited references. This has been considered but not found persuasive. In response to applicant's argument, the test for obviousness is not whether the features of a secondary reference are bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
In the instant case, Mori et al teach that cells which have metastatic potential are present in the culture of cancer cells of various types, leading one of skill in the art to collect and analyze cells having metastatic potential that survived a chemotherapy treatment. One of skill in the art would understand that the anchorage independent cells, such as “floaters” or cells easily detached from semi-solid medium would comprise apoptotic cells and cell with metastatic potential. One of skill in the art would understand that culture of the anchorage-independent cells remaining after exposure to a chemotherapeutic agent would eliminate the dying apoptotic cells and serve to propagate the cells with metastatic potential which can then be screened for susceptibility to different chemotherapy drugs. The motivation for the second culture to identify the anti-metastatic drug of choice are well-known in the art, but can be exemplified by Shi et al who teach that approximately 50% of patients with local breast tumors develop metastases.
The provisional rejection of claims 1 and 4-6 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) is withdrawn in light of applicant’s Terminal Disclaimer.
All claims are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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.
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, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
Prosecution Insights