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 .
DETAILED ACTION
This Office Action is a response to Applicant’s Amendment and Remarks filed February 18, 2026.
Claims 7, 15 and 23 have been canceled. Claims 1, 8, 9, 16, 17 and 24 have been amended.
Claims 1, 5, 6, 8, 9, 13, 14, 16, 17, 21, 22, 24 and 25 are pending in the instant application.
Claims 1, 5, 6, 8, 9, 13, 14, 16, 17, 21, 22, 24 and 25 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 102
In the previous Office Action mailed November 18, 2025, claims 9 and 13-16 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Choi et al. (Cancer Res (2014) 74 (19_Supplement): 2, Abstract). This rejection is moot against claim 15 in view of Applicant’s Amendment filed November 18, 2025 to cancel this claim. This rejection is withdrawn against the remaining claims in view of Applicants Amendment to the claims filed November 18, 2025.
Claim Rejections - 35 USC § 103
In the previous Office Action mailed November 18, 2025, claims 1 and 5-8 were rejected under 35 U.S.C. 103 as being unpatentable over Choi et al. (Cancer Res (2014) 74 (19_Supplement): 2, Abstract). This rejection is moot against claim 7 in view of Applicant’s Amendment filed November 18, 2025 to cancel this claim. This rejection is withdrawn against the remaining claims in view of Applicants Amendment to the claims filed November 18, 2025.
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In the previous Office Action mailed November 18, 2025, claims 17 and 21-25 were rejected under 35 U.S.C. 103 as being unpatentable over Choi et al. (Cancer Res (2014) 74 (19_Supplement): 2, Abstract) in view of McGuire et al. (New Engl J Med. 1996 Jan 4;334(1):1-6). This rejection is moot against claim 23 in view of Applicant’s Amendment filed November 18, 2025 to cancel this claim. This rejection is withdrawn against the remaining claims in view of Applicants Amendment to the claims filed November 18, 2025.
Applicant's amendment to the claims filed February 18, 2026 necessitated the new ground(s) of rejection presented below:
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 9, 13, 14 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mishra et al. (J Surg Res. 2015 February; 193(2): 745-753).
The claims are drawn to a composition for alleviating resistance to a platinum-based chemotherapy in a subject, comprising a therapeutic agent capable of alleviating resistance to the platinum-based chemotherapeutic agent, the therapeutic agent comprising (i) an siRNA that inhibits ITGB4 expression, or (ii) an siRNA that inhibits ITGB4 expression and an siRNA that inhibits PXN expression, wherein the subject has developed or is at an elevated risk of developing resistance to the platinum-based chemotherapy.
Mishra et al. teach a therapeutic agent comprising an siRNA that inhibits ITGB4 expression. See Mishra et al. at page 4, (2.7) ITGB4 small interfering RNA (siRNA) transfection.
While Mishra et al. does not explicitly identify the siRNA that inhibits ITGB4 expression as a composition for alleviating resistance to a platinum-based chemotherapy in a subject, Applicant is reminded that a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Furthermore, the Examiner is interpreting the siRNA that inhibits ITGB4 expression of Mishra et al. as ”capable of” alleviating resistance to a platinum-based chemotherapeutic agent, absent some evidence to the contrary.
Further, the limitation of alleviating resistance to a platinum-based chemotherapy in a subject is nothing more than an intended use. The intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, the siRNA that inhibits ITGB4 expression taught and suggested by Mishra et al. is capable of alleviating resistance to a platinum-based chemotherapeutic agent in a subject and therefore meets the functionality reported in the present application, absent some evidence to the contrary.
Therefore, claims 9, 13, 14 and 16 are anticipated by Mishra et al.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
Claims 1, 5, 6, 8, 17, 21, 22, 24 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (Scientific Reports, Vol. 9: No. 5039, 2019 Mar 25, pages 1-14).
Claims 1, 5, 6 and 8 are drawn to a method of alleviating resistance to a platinum-based chemotherapy administered to a subject, comprising administering to the subject a composition, the composition comprising a therapeutic agent, the therapeutic agent comprising (i) an siRNA that inhibits integrin b4 (ITGB4) expression, (ii) an siRNA that inhibits ITGB4 expression and an siRNA that inhibits paxillin (PXN) expression, or (iii) a compound selected from carfilzomib, ixazomib. and CUDC-101, wherein the subject has developed or is at an elevated risk of developing resistance to the platinum-based chemotherapy. Claims 17, 21, 22, 24 and 25 are drawn to a method of treating cancer in a subject, comprising administering to the subject: a platinum-based chemotherapeutic agent, and a composition comprising a therapeutic agent capable of alleviating resistance to the platinum-based chemotherapeutic agent, the therapeutic agent comprising (i) an siRNA that inhibits ITGB4 expression,(ii) an siRNA that inhibits ITGB4 expression and an siRNA that inhibits PXN expression, or (iii) a compound selected from carfilzomib, ixazomib, and CUDC-101, wherein the subject has developed or is at an elevated risk of developing resistance to the platinum-based chemotherapy.
Lee et al. teach carfilzomib (CFZ) enhances cisplatin (Cis) induced apoptosis in SK-N BE(2)-M17 human neuroblastoma cells. See Abstract.
Lee et al. also teach that CFZ can be used in combination therapy for patients with neuroblastoma to overcome the resistance and adverse side effects of Cis. Lee et al. further teach CFZ can be utilized in combination with Cis and CFZ can exert a chemosensitization effect in Cis-resistant neuroblastoma cells.
Lee et al. conclude with the effects of CFZ and Cis are additive in terms of cell cycle arrest, apoptotic cell death, and ER stress, co-treatment of CFZ with Cis might reduce the individual dosages of CFZ and Cis, resulting in lower side effects and overcoming of drug resistance. Therefore, a combination therapy with CFZ and Cis might be beneficial for the treatment neuroblastoma, a cancerous tumor that begins in the nerve tissue of infants and young children.
In all, the Lee study demonstrates that CFZ enhances the effectiveness of Cis in killing neuroblastoma cells, wherein the combination treatment works synergistically, increasing apoptosis and enhancing cell cycle arrest, suggesting a promising strategy to overcome cisplatin resistance.
Regarding those claims that recite that the subject has developed or is at risk of developing resistance to platinum-based chemotherapy, it should be noted that any subject with a malignant cancer, such as neuroblastoma is at an elevated risk of developing resistance to chemotherapy.
Concerning claim 25 which recites, “wherein the chemotherapeutic agent is administered at a reduced dose comparing to the dose of the chemotherapeutic agent when administered alone”, Applicant is reminded that it is held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See In re Aller, 105 USPQ 233. Furthermore, during the course of routine experimentation and optimization, the skilled artisan would have expected reasonable success of administering the chemotherapeutic agent at a reduced dose comparing to the dose of the chemotherapeutic agent when administered alone as presently claimed, absent evidence to the contrary.
Before the effective filing date of the claimed invention, a method of alleviating resistance to cisplatin chemotherapy comprising administering a therapeutic agent comprising carfilzomib was taught and suggested in the prior art of Lee et al. Additionally, before the effective filing date of the claimed invention, a method of treating cancer comprising administering cisplatin and a therapeutic agent comprising carfilzomib was taught and suggested in the prior art of Lee et al.
It would have been obvious and one of skill in the art would have been motivated to modify the in vitro reports of Lee et al. to devise a method of alleviating resistance to cisplatin chemotherapy in a subject comprising administering a therapeutic agent comprising carfilzomib since Lee et al. make it clear that their research is applicable for human therapy. Additionally, it would have been obvious and one of skill in the art would have been motivated to modify the in vitro examples of Lee et al. to devise a method of treating cancer comprising administering cisplatin and a therapeutic agent comprising carfilzomib since Lee et al. are explicit that their research makes for a good treatment strategy for patients with neuroblastoma.
A person of ordinary skill in the art would have expected reasonable success of devising the method steps of Applicant's claimed invention using the teachings, suggestions and motivation of Lee et al.
Therefore, the subject matter of claims 1, 5, 6, 8, 17, 21, 22, 24 and 25 is obvious over Lee et al.
Claim Rejections - Improper Markush Grouping
Claims 1, 5, 6, 8, 17, 21, 22, 24 and 25 are rejected on the basis that the claims contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination of process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP §706.03(y).
The Markush grouping in the claims are improper because the alternatives defined by the Markush grouping do not share a single structural similarity and a common use flowing from the shared structural similarity. For example, the therapeutic agent comprising (i) an siRNA that inhibits integrin b4 (ITGB4) expression, (ii) an siRNA that inhibits ITGB4 expression and an siRNA that inhibits paxillin (PXN) expression, or (iii) a compound selected from carfilzomib, ixazomib. and CUDC-101 used in the methods as claimed are entirely different compositions (e.g. nucleic acid vs. small compound molecule). The compositions of the invention do not share a single structural similarity and a common use that flows from the structural similarity feature.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternatives within a single claim in fact share a single structural similarity as well as a common use.
This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
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 Terra C. Gibbs whose telephone number is 571-272-0758. The examiner can normally be reached from 8 am - 5 pm M-F.
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/TERRA C GIBBS/ Primary Examiner, Art Unit 1635