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 .
Response and Amendment Filed
Applicant’s response and amendment, filed March 9, 2026, has been entered and made of record. Accordingly, the status of the claims is as follows: Claims 1, 2, 4 and 11-13 are amended; claims 3 and 6-10 are unamended; claim 5 is canceled.
Previously Set Forth Objections and Rejections
All of the objections and rejections set forth in the previous Office action (mailed October 9, 2025) are hereby withdrawn.
The following new grounds of rejection are set forth:
Claim Rejections - 35 USC § 103
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 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, 4, 9 and 10-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Morrison et al. (U.S. Patent Application Publication No. WO 2012/0143167) in view of Enam et al. (PCT Publication No. WO 2021/076962).
In regard to claims 1, 4 and 12, Morrison et al. teach a process for increasing the efficacy of cancerous disease inhibiting therapeutic agents (chemotherapy) delivered to a treatment region of a tissue structure, such as a tumor, by using tumor hypothermia in combination with the chemotherapy to induce tumor necrosis and/or inhibition of tumor growth (see paras. 0026 and 0032-0033). Morrison et al. also teach the use of the process with tumor tissue lacking p53 expression (p53 mutation) (see paras. 0029, 0089 and 0101). Morrison et al. teach focal (tumor) and/or whole body hypothermia (would include peripheral cooling) (see para. 0064) and defines “hypothermic treatment” as any cold exposure event including cold exposure resulting in tissue temperatures in the range of -21 degrees C to 37 degrees C that are effective for reduction of microvasculature blood flow and sensitization to chemotherapy (see para. 0043). Morrison is silent as to the duration of the hypothermic treatment. However, Enam et al. teach a similar method of treating a cancerous tumor using induced hypothermia and chemotherapy (see paras. 0065 and 0069) where a 24 hour application of the hypothermic is disclosed for effective treatment of the cancerous tumor (see paras. 0059 and 0097). Enam et al. thus demonstrate that the art is well aware of the use of a 24 hour duration for application of induced hypothermia. Accordingly, it would have been obvious for one of ordinary skill in the art at the effective filing date of the invention to make the duration of the hypothermic treatment in Morrison et al. 24 hours, as taught by Enam et al., for effective treatment of the cancerous tumor. In regard to claims 9 and 10, see para. 0085 of Morrison et al. In regard to claim 11, Morrison et al. teach the use of a cryoprobe 10 (see Fig. 7 and para. 0081). In regard to claim 13, see para. 0068 of Morrison et al.
Claim(s) 2 and 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Morrison et al. (PCT Publication No. WO 2012/0143167) in view of Enam et al. (PCT Publication No. WO 2021/076962) and further in view of Kruezer et al. (“Hypothermia associated with antipsychotic drug use: a clinical case series and review of current literature”; Journal of Clinical Pharmacology, Vol. 52, No. 7, (2012), pp. 1090-1097 – hereinafter “Kruezer et al.”).
In regard to claims 2 and 3, Morrison et al. are silent as to inducing hypothermia by administering an anti-psychotic drug. However, Kruezer et al. teach that an anti-psychotic drug, such as olanzapine and benperidol, can induce hypothermia (see Abstract). Accordingly, it would have been obvious for one of ordinary skill in the art at the effective filing date of the invention to administer an anti-psychotic drug, such as olanzapine and benperidol, in order to induce hypothermia in the method disclosed by Morrison et al.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Morrison et al. (PCT Publication No. WO 2012/0143167) in view of Enam et al. (PCT Publication No. WO 2021/076962) and further in view of Flaman et al., “A simple p53 functional assay for screening cell lines, blood and tumors, Proc. Natl, Acad. Sci., Vol. 92 (1995), pp. 3963-3967 – hereinafter “Flaman et al.”).
In regard to claim 6, Morrison et al. are silent as to assaying a sample from the subject. However, Flaman et al. teach assaying a sample from a subject for a ts p53 mutation (see Abstract). It would have been obvious for one of ordinary skill in the art at the effective filing date of the invention to modify the tumor treatment of Morrison et al. to include the step of assaying a sample, as disclosed by Flaman et al., as it provides the benefit of detecting the p53 mutations implicated in the pathogenesis of half of all human tumors.
Claim(s) 7 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Morrison et al. (PCT Publication No. WO 2012/0143167) in view of Enam et al. (PCT Publication No. WO 2021/076962) and further in view of Flaman et al., “A simple p53 functional assay for screening cell lines, blood and tumors, Proc. Natl, Acad. Sci., Vol. 92 (1995), pp. 3963-3967 – hereinafter “Flaman et al.”) and further in view of Hollstein et al. (p53 Mutations in Human Cancers; Science, Vol. 253, July 5, 1992, pp 49-53 – hereinafter “Hollstein et al.”).
In regard to claims 7 and 8, Morrison et al. is silent as to the specifics of the ts p53 mutation. However, Hollstein et al. teach that numerous amino acids can alter the biological function of the p53 protein (see pages 50-51). Accordingly, it would have been obvious to one of ordinary skill in the art at the effective filing date of the invention that the method of Morrison et al. could be used to treat any of the ts p53 mutations described by Hollstein et al. as Morrison et al. clearly teach treating tumors with p53 mutations (see above).
Response to Arguments
Applicant’s arguments, filed March 9, 2026, with respect to the rejection(s) of claim(s) based upon Fox have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made, as set forth above.
Conclusion
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 BEVERLY MEINDL FLANAGAN whose telephone number is (571)272-4766. The examiner can normally be reached Mon-Fri 7:30AM to 5:00PM.
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/BEVERLY M FLANAGAN/Primary Examiner, Art Unit 3794
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